Systems and methods for monitoring energy application to denervate a pulmonary artery

ABSTRACT

A catheter system for ablation of tissue around a blood vessel, e.g., the pulmonary artery, to reduce neural activity of nerves surrounding the blood vessel. The catheter system includes an elongate shaft having a proximal portion coupled to a handle, and a distal portion. The distal portion includes a transducer and an expandable anchor, which may be actuated to transition between a collapsed delivery state and an expanded deployed state where the anchor centralizes the transducer within the blood vessel. The transducer may be actuated to emit energy to reduce neural activity of the nerves surrounding the blood vessel. Systems and method are further provided for confirming that neural activity of the nerves surround the blood vessel has been sufficiently reduced.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation application of International PCTPatent Appl. No. PCT/IB2022/055854, filed Jun. 23, 2022, which claimspriority to EP Patent Appl. No. 21305873.8, filed Jun. 24, 2021, theentire contents of each of which are incorporated herein by reference.

FIELD OF USE

The present disclosure is directed generally to medical devices,systems, and methods for applying energy to reduce neural activity in ablood vessel such as the pulmonary artery to treat pulmonaryhypertension and/or other pulmonary vascular disorders.

BACKGROUND

Pulmonary hypertension is a disease phenomenon of multifactorialetiology with high morbidity and mortality. The disease causes increasedwork for the right side of the heart and eventually hypertrophy anddysfunction of not only the right side of the heart, but often the leftside as well. The prognosis of pulmonary hypertension historically hasbeen poor, with median survival historically being less than 3 years.Currently, with the advent of new pharmacologic therapies, survival hasimproved to 50 to 60% at 5 years. However, many patients continue toprogress to worsening stages of pulmonary hypertension, and despiteimprovements in therapy, prognosis for the condition remains grave.

In view of the foregoing drawbacks of previously known systems andmethods, there exists a need for improved systems and methods fortreating pulmonary hypertension, particularly minimally invasivetreatments that would reduce or negate the need for pharmaceuticalremedies, and/or would be permanent or at least long-lasting.

Treatment of pulmonary hypertension via intravascular denervation of thepulmonary artery was first described in U.S. Pat. No. 9,005,100 toGnanashanmugam, the entire contents of which are incorporated herein byreference. It would be desirable to provide further systems fordenervating a blood vessel such as the pulmonary artery, as well assystems for verifying that the denervation has been completed.

SUMMARY

The present disclosure overcomes the drawbacks of previously-knownsystems and methods for reducing pulmonary hypertension by providingsystems and methods for interrupting the nerves (e.g., sympatheticnerves) around and/or innervating the left, right, and/or main pulmonaryarteries. Neuromodulation may be accomplished via ablation, denervation,which may or may not be reversible, stimulation, etc. For example,systems disclosed herein are configured to navigate a catheter from aremote insertion point, through the heart, and into the pulmonary brancharteries and trunk. The catheter may include an anchor that, whendeployed, will anchor and centralize a transducer within the vessel wallat a target ablation site. Once the nerves located at the ablation sitehave been ablated, the anchor may be collapsed, and the transducer maybe repositioned at another ablation site within the vessel. This deploy,ablate, collapse, and move method may be repeated until both pulmonaryartery branches and the pulmonary trunk have been ablated.

In accordance with one aspect of the present disclosure, a system forreducing neural activity of nerves around a blood vessel of a patient isprovided. The system may include a handle, an inner catheter, atransducer assembly, an outer catheter, an expandable anchor, and asheath. For example, the inner catheter may include a guidewire lumenextending through at least a portion of a length of the inner catheter,and a proximal region of the inner catheter operatively coupled to thehandle. The transducer assembly may include a transducer shaft having anultrasound transducer coupled thereto. The ultrasound transducer may beactuated to emit ultrasonic energy within the blood vessel to reduceneural activity of nerves around the blood vessel. The transducer shaftmay include a lumen sized and shaped to slidably receive the innercatheter therein, and a proximal region operatively coupled to thehandle. The outer catheter may include a lumen sized and shaped toreceive the transducer shaft therein, and a proximal region operativelycoupled to the handle. The expandable anchor may include a distal endcoupled to the inner catheter and a proximal end coupled to the outercatheter such that relative movement between the inner catheter and theouter catheter causes the expandable anchor to transition between acollapsed delivery state and an expanded deployed state. Moreover, theexpandable anchor may centralize the ultrasound transducer within theblood vessel of the patient in the expanded deployed state. The sheathmay include a lumen sized and shaped to slidably receive the outercatheter and the expandable anchor in the collapsed delivery statetherein. A distal region of the sheath may have a stiffness sufficientto facilitate transitioning of the expandable anchor from the expandeddeployed state to the collapsed delivery state upon movement of thedistal region of the sheath relative to the expandable anchor withoutbuckling the distal region of the sheath, and a proximal region of thesheath operatively coupled to the handle. The blood vessel may be apulmonary artery and the ultrasound transducer may be actuated to emitultrasonic energy within the pulmonary artery to reduce neural activityof nerves around the pulmonary artery to treat pulmonary hypertension.

The system further may include a separation sleeve having a lumen sizedand shaped to slidably receive the sheath therein, and a proximal regionof the separation sleeve fixedly coupled to the handle. In addition, thesystem may include an introducer having a lumen sized and shaped toslidably receive the sheath and the separation sleeve therein. Forexample, the introducer may be fixed relative to the patient andactuated to prevent relative movement between the separation sleeve andthe introducer, such that the sheath is movable relative to theseparation sleeve without relative movement between the transducerassembly and the patient. Moreover, the introducer may include a valvedisposed within the lumen of the introducer, such that the introducermay be actuated to prevent relative movement between the separationsleeve and the introducer by actuating the valve against the separationsleeve when the separation sleeve is disposed within the lumen of theintroducer.

A distal end of the inner catheter may include an atraumatic tip. Forexample, the atraumatic tip may include a tapered profile, such that across-sectional area of the atraumatic tip decreases from a proximal endof the atraumatic tip toward a distal end of the atraumatic tip. In adelivery configuration, a distal end of the sheath abuts the atraumatictip. Moreover, the distal end of the expandable anchor may be coupled tothe inner catheter via a ring slidably disposed on the inner catheter,such that the distal end of the expandable anchor is slidably coupled tothe inner catheter. The outer catheter may be fixedly coupled to thehandle, and the inner catheter may be actuated to move relative to theouter catheter to cause the expandable anchor to transition between thecollapsed delivery state and the expanded deployed state. Alternatively,the inner catheter may be fixedly coupled to the handle, and the outercatheter may be actuated to move relative to the inner catheter to causethe expandable anchor to transition between the collapsed delivery stateand the expanded deployed state.

The expandable anchor may include a plurality of struts, e.g., aplurality of diamond-shaped struts. The expandable anchor may be formedof a shape-memory material. Moreover, the expandable anchor may have aradial force in the expanded deployed state that is greater than astiffness force of the inner catheter, the transducer shaft, the outercatheter, and the distal region of the sheath. In addition, thestiffness of the distal region of the sheath may be greater than astiffness of the proximal region of the sheath. An outer diameter of thedistal region of the sheath may be larger than an outer diameter of theproximal region of the sheath. The transducer shaft and the outercatheter may be sealed to create a fluidically sealed cavitytherebetween, such that at least one cable may be disposed in thefluidically sealed cavity to provide electrical energy to the ultrasoundtransducer for emitting the ultrasonic energy.

The system further may include a generator operatively coupled to theultrasound transducer. The generator may be actuated to provideelectrical energy to the ultrasound transducer to cause the ultrasoundtransducer to emit ultrasonic energy. In addition, the system mayinclude a sensor that may measure temperature of the ultrasoundtransducer, and the generator may include a control loop programmed toadapt the electric energy provided to the ultrasound transducer if thetemperature of the ultrasound transducer exceeds a predeterminedthreshold. Additionally, the transducer may convert acoustic energyreflected from an adjacent anatomical airway structure to electricalenergy, and the generator may include a control loop programmed to stopemission of ultrasonic energy if the electrical energy exceeds apredetermined threshold, wherein the electrical energy is indicative ofa level of acoustic energy reflected from the adjacent anatomical airwaystructure.

The system further may include one or more pacing electrodes disposed onthe expandable anchor. The one or more pacing electrodes may be actuatedto pace the blood vessel and induce a physiological response from thepatient if a phrenic nerve is located around the blood vessel. Inaddition, the system may include a distension mechanism that may apply aforce to an inner wall of the blood vessel sufficient to distend theblood vessel and stimulate baroreceptors within the blood vessel. Thedistension mechanism may include an expandable member that may beexpanded from a collapsed state to an expanded state where theexpandable member applies the force to the inner wall of the bloodvessel. Alternatively, the distension mechanism may include a torqueingmechanism that may be actuated to bend an elongated shaft of the systemwithin the blood vessel to apply the force to the inner wall of theblood vessel.

Moreover, the system further may include a controller operativelycoupled to one or more sensors that may measure pressure within theblood vessel. The controller may be programmed to: receive firstpressure information within the blood vessel from the one or moresensors at a first time; receive second pressure information within theblood vessel from the one or more sensors at a second time while theexpandable member applies a first force to the inner wall to distend theblood vessel; receive third pressure information within the blood vesselfrom the one or more sensors at a third time after ultrasonic energy isemitted within the blood vessel via the ultrasound transducer to reduceneural activity of nerves around the blood vessel and while theexpandable member applies a second force to the inner wall to distendthe blood vessel; and compare the second pressure information to thethird pressure information to determine whether the ultrasonic energyhas reduced neural activity of the nerves around the blood vessel.

For example, the second pressure information may be indicative of afirst pressure gradient between pressure within the blood vessel whilethe first force is applied to the inner wall to distend the blood vesseland pre-distension pressure within the blood vessel associated with thefirst pressure information, and the third pressure information may beindicative of a second pressure gradient between pressure within theblood vessel while the second force is applied to the inner wall todistend the blood vessel and pre-distension pressure within the bloodvessel associated with the first pressure information. Accordingly, theultrasonic energy may have reduced neural activity of the nerves aroundthe blood vessel if the comparison of the second and third pressureinformation indicates that the second pressure gradient is less than thefirst pressure gradient by more than a predetermined threshold. Thesystem further may include one or more sensors that may measure pressurewithin the blood vessel.

The system further may include a transducer catheter having a lumensized and shaped to receive the transducer shaft therein and a proximalregion operatively coupled to the handle, such that the transducercatheter slidably disposed within the outer catheter. In thisconfiguration, the transducer shaft and the transducer catheter aresealed to create a fluidically sealed cavity therebetween, such that atleast one cable may be disposed in the fluidically sealed cavity toprovide electrical energy to the ultrasound transducer for emittingultrasonic energy.

The handle may be actuated to cause translational movement of theultrasound transducer relative to the inner catheter and the outercatheter via the transducer shaft and the transducer catheter. At leastone of the inner catheter, the outer catheter, and the sheath mayinclude a guidewire port sized and shaped to receive the guidewiretherethrough. The system further may include one or more intravascularultrasound (IVUS) transducers disposed on at least one of the innercatheter distal to the ultrasound transducer, the outer catheter betweenthe ultrasound transducer and the proximal end of the expandable anchor,or the outer catheter proximal to the proximal end of the expandableanchor. The one or more IVUS transducers may generate data for detectinganatomical structures adjacent to the blood vessel within a field ofview of the one or more IVUS transducers. The one or more IVUStransducers may include a shield for masking at least a portion of theultrasonic energy emitted from the one or more IVUS transducers.

In addition, the system may include a torque shaft having a lumen sizedand shaped to receive the inner catheter therein and a proximal regionoperatively coupled to the handle. The torque shaft may be coupled tothe ultrasound transducer and may be actuated to cause rotation of theultrasound transducer relative to the inner catheter. The ultrasoundtransducer may include a plurality of transducer segments, and eachtransducer segment of the plurality of transducer segments may beindependently actuatable to selectively emit ultrasonic energy.

In accordance with another aspect of the present disclosure, a methodfor reducing neural activity of nerves around a blood vessel of apatient is provided. The method may include selecting a catheter systeminclude a handle, an inner catheter having a guidewire lumen, atransducer assembly slidably disposed over the inner catheter, an outercatheter disposed over a transducer shaft of the transducer assembly, anexpandable anchor having a distal end coupled to the inner catheter anda proximal end coupled to the outer catheter, and a sheath slidablydisposed over the outer catheter. The method further may includeadvancing a distal end of a guidewire to a target location within theblood vessel; advancing the catheter system over a proximal end of theguidewire via the guidewire lumen until an ultrasound transducer of thetransducer assembly is in the target location within the blood vessel,the expandable anchor disposed within the sheath in a collapsed deliverystate; retracting the sheath to expose the expandable anchor within theblood vessel; moving the inner catheter and the outer catheter relativeto each other to cause the expandable anchor to transition from thecollapsed delivery state to an expanded deployed state, the expandableanchor centralizing the ultrasound transducer within the blood vessel inthe expanded deployed state; actuating the ultrasound transducer to emitultrasonic energy within the blood vessel to reduce neural activity ofnerves around the blood vessel; moving the inner catheter and the outercatheter relative to each other to cause the expandable anchor totransition from the expanded deployed state to the collapsed deliverystate; advancing the sheath over the expandable anchor in the collapseddelivery state, a distal region of the sheath having a stiffnesssufficient to facilitate transitioning of the expandable anchor from theexpanded deployed state to the collapsed delivery state upon movement ofthe distal region of the sheath relative to the expandable anchorwithout buckling the distal region of the sheath; and removing thecatheter system from the patient.

Advancing the catheter system over the proximal end of the guidewire viathe guidewire lumen until the ultrasound transducer is in the targetlocation within the blood vessel may include advancing the cathetersystem over the proximal end of the guidewire via the guidewire lumenuntil the ultrasound transducer is in the target location within apulmonary artery. The method further may include inserting an introducerin a vasculature of the patient such that the introducer is fixedrelative to the patient, such that advancing the catheter system overthe proximal end of the guidewire includes advancing the catheter systemover the proximal end of the guidewire and through the introducer.

In addition, the method may include actuating a valve disposed within alumen of the introducer against a separation sleeve of the cathetersystem to prevent relative movement between the separation sleeve andthe introducer such that the sheath is movable relative to theseparation sleeve without relative movement between the transducerassembly and the patient. Accordingly, the separation sleeve may beslidably disposed over at least a portion of the sheath and fixedlycoupled to the handle. The method further may include moving theultrasound transducer translationally relative to the expandable anchorin the expanded deployed state within the blood vessel.

In addition, the method may include, prior to removing the cathetersystem from the patient, advancing the catheter system until theultrasound transducer is in a second target location within anotherportion of the blood vessel; retracting the sheath to expose theexpandable anchor within the another portion of the blood vessel; movingthe inner catheter and the outer catheter relative to each other tocause the expandable anchor to transition from the collapsed deliverystate to the expanded deployed state within the another portion of theblood vessel; and actuating the ultrasound transducer to emit ultrasonicenergy within the another portion of the blood vessel to reduce neuralactivity of nerves around the another portion of the blood vessel.Actuating the ultrasound transducer to emit ultrasonic energy within theblood vessel may include actuating the ultrasound transducer inaccordance with a predetermined actuation regime. The predeterminedactuation regime may include predetermined periods of non-ablationbetween predetermined periods of ablation.

Moreover, the method may include, prior to actuating the ultrasoundtransducer to emit ultrasonic energy within the blood vessel, pacing theblood vessel via one or more pacing electrodes disposed on theexpandable anchor in the expanded deployed state to induce an observablephysiological response from the patient if a phrenic nerve is locatedaround the blood vessel; and not actuating the ultrasound transducer toemit ultrasonic energy at the target location within the blood vessel ifthe physiological response is observed to avoid damaging the phrenicnerve. Additionally, or alternatively, the method may include pacing theblood vessel via one or more pacing electrodes disposed on theexpandable anchor in the expanded deployed state to induce an observablephysiological response from the patient if a phrenic nerve is locatedaround the blood vessel while ultrasonic energy is emitted within theblood vessel; and stopping emission of ultrasonic energy within theblood vessel if a change in the physiological response observed overtime exceeds a predetermined threshold to avoid damaging the phrenicnerve.

In accordance with another aspect of the present invention, anothermethod for reducing neural activity of nerves around a blood vessel of apatient is provided. The method may include measuring first pressureinformation within the blood vessel; applying a first force to an innerwall of the blood vessel to distend the blood vessel; measuring secondpressure information within the blood vessel while the first force isapplied to the inner wall to distend the blood vessel; emitting energyvia an ablation device positioned within the blood vessel to ablatenerves around the blood vessel; applying a second force to the innerwall of the blood vessel to distend the blood vessel; measuring thirdpressure information within the blood vessel while the second force isapplied to the inner wall to distend the blood vessel; and comparing thesecond pressure information to the third pressure information todetermine whether the emitted energy has reduced neural activity of thenerves around the blood vessel.

The second pressure information may be indicative of a first pressuregradient between pressure within the blood vessel while the first forceis applied to the inner wall to distend the blood vessel andpre-distension pressure within the blood vessel associated with thefirst pressure information, and the third pressure information may beindicative of a second pressure gradient between pressure within theblood vessel while the second force is applied to the inner wall todistend the blood vessel and pre-distension pressure within the bloodvessel associated with the first pressure information. The emittedenergy may have reduced neural activity of the nerves around the bloodvessel if the comparison of the second and third pressure informationindicates that the second pressure gradient is less than the firstpressure gradient by more than a predetermined threshold. Additionallyor alternatively, the emitted energy may have reduced neural activity ofthe nerves around the blood vessel if the second pressure gradient iszero.

Applying the first and second force to the inner wall of the bloodvessel to distend the blood vessel may include applying a forcesufficient to stimulate baroreceptors within the blood vessel. Moreover,applying at least one of the first or second force to the inner wall ofthe blood vessel to distend the blood vessel may include expanding anexpandable member from a collapsed state to an expanded state, theexpandable member disposed on a catheter sized and shaped to bepositioned within the blood vessel. In the expanded state, theexpandable device may not fully occlude blood through the blood vessel.The ablation device may be disposed on the same catheter as theexpandable member. Alternatively, the ablation device may be disposed ona second catheter sized and shaped to be positioned within the vessel,such that the second catheter is different from the catheter.Alternatively, applying at least one of the first or second force to theinner wall of the blood vessel to distend the blood vessel may includeapplying a torque to a catheter shaft to bend the catheter shaft withinthe blood vessel to apply the force.

If the emitted energy has not reduced neural activity of the nervesaround the blood vessel based on the comparison of the second and thirdpressure information, the method further include: emitting energy viathe ablation device positioned within the blood vessel to ablate nervesaround the blood vessel; applying a third force to the inner wall of theblood vessel to distend the blood vessel; measuring fourth pressureinformation within the blood vessel while the third force is applied tothe inner wall to distend the blood vessel; and comparing the fourthpressure information to at least one of the second or third pressureinformation to determine whether the emitted energy has reduced neuralactivity of the nerves around the blood vessel. Moreover, emittingenergy via the ablation device positioned within the blood vessel toablate nerves around the blood vessel may include emitting at least oneof focused ultrasound, unfocused ultrasound, radio frequency, microwave,cryo energy, laser, or pulsed field electroporation. The method furthermay include deploying an expandable anchor within the vessel tocentralize the ablation device within the vessel.

In accordance with another aspect of the present disclosure, anothersystem for reducing neural activity of nerves around a blood vessel of apatient is provided. The system may include a catheter assembly, adistension mechanism, one or more sensors that may measure pressurewithin the blood vessel, and a controller operatively coupled to the oneor more sensors. The catheter assembly may have a proximal regionoperatively coupled to a handle and a distal region sized and shaped tobe positioned within the blood vessel, and the distal region of thecatheter assembly may include an ablation device that may be actuated toemit energy within the blood vessel to reduce neural activity of nervesaround the blood vessel. The distension mechanism may be actuated toapply a force to an inner wall of the blood vessel sufficient to distendthe blood vessel and stimulate baroreceptors within the blood vessel.

The controller may be programmed to: receive first pressure informationwithin the blood vessel from the one or more sensors at a first time;receive second pressure information within the blood vessel from the oneor more sensors at a second time while the distension mechanism appliesa first force to the inner wall to distend the blood vessel; receivethird pressure information within the blood vessel from the one or moresensors at a third time after ultrasonic energy is emitted within theblood vessel via the ultrasound transducer to reduce neural activity ofnerves around the blood vessel and while the distension mechanismapplies a second force to the inner wall to distend the blood vessel;and compare the second pressure information to the third pressureinformation to determine whether the ultrasonic energy has reducedneural activity of the nerves around the blood vessel.

The distension mechanism may include an expandable member that may beexpanded from a collapsed state to an expanded state to apply the forceto the inner wall of the blood vessel. Alternatively, the distensionmechanism may include a torqueing mechanism configured to bend a shaftof the catheter assembly within the blood vessel to apply the force tothe inner wall of the blood vessel. The system further may include anexpandable anchor that may transition between a collapsed delivery stateand an expanded deployed state where the expandable anchor centralizesthe ablation device within the blood vessel. Moreover, the ablationdevice may emit at least one of focused ultrasound, unfocusedultrasound, radio frequency, microwave, cryo energy, laser, or pulsedfield electroporation.

In accordance with another aspect of the present disclosure, a systemfor reducing neural activity of nerves around a pulmonary artery of apatient is provided. The system may include a handle, an elongatedshaft, an ultrasound transducer, and an expandable anchor. The elongatedshaft may have a proximal region operatively coupled to the handle, anda distal region. The ultrasound transducer may be disposed on the distalregion of the elongated shaft, and may be actuated to emit ultrasonicenergy within the pulmonary artery to reduce neural activity of nervesaround the pulmonary artery. The expandable anchor may be disposed onthe distal region of the elongated shaft, and may transition between acollapsed delivery state and an expanded deployed state where theexpandable anchor centralizes the ultrasound transducer within thepulmonary artery of the patient.

The expandable anchor may include a plurality of struts having roundededges configured to prevent damage to the pulmonary artery. The systemfurther may include a sheath having a lumen sized and shaped to slidablyreceive the elongated shaft and the expandable anchor in the collapseddelivery state therein. A distal region of the sheath may have astiffness sufficient to facilitate transitioning of the expandableanchor from the expanded deployed state to the collapsed delivery stateupon movement of the distal region of the sheath relative to theexpandable anchor without buckling the distal region of the sheath, anda proximal region of the sheath operatively coupled to the handle. Theultrasound transducer may emit the ultrasonic energy within a mainbranch of the pulmonary artery, a right branch of the pulmonary artery,or a left branch of the pulmonary artery, or any combination thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a perspective view of an exemplary catheter system fortreating tissue constructed in accordance with the principles of thepresent disclosure.

FIG. 1B is a schematic cross-sectional view of the catheter system ofFIG. 1A.

FIG. 2A illustrates the distal region of the catheter system of FIG. 1A.

FIG. 2B illustrates an exemplary expandable anchor constructed inaccordance with the principles of the present disclosure.

FIG. 2C illustrates an exemplary sheath constructed in accordance withthe principles of the present disclosure.

FIG. 3 is a perspective view of an exemplary handle of the cathetersystem of FIG. 1A constructed in accordance with the principles of thepresent disclosure.

FIG. 4A is a cross-sectional view of the catheter system of FIG. 1A, andFIGS. 4B to 4E are close-up views of the handle of FIG. 4A.

FIG. 5A illustrates the catheter system of FIG. 1A in a deliveryconfiguration.

FIG. 5B illustrates the catheter system of FIG. 1A in a deployedconfiguration.

FIGS. 6A to 6D are various views of an exemplary transducer assemblyconstructed in accordance with the principles of the present disclosure.

FIG. 7 is a flow chart of an exemplary method for treating tissue inaccordance with the principles of the present disclosure.

FIG. 8 is a schematic illustrating positioning of the catheter system ofFIG. 1A within a patient in accordance with the principles of thepresent disclosure.

FIG. 9 is a flow chart of an exemplary method for confirming reductionof neural activity of nerves in accordance with the principles of thepresent disclosure.

FIG. 10 is a distributivity plot diagram illustrating energy emissionintensity.

FIG. 11 illustrates the distal region of an alternative exemplarycatheter system having guidewire ports constructed in accordance withthe principles of the present disclosure.

FIG. 12 is a cross-sectional view of an alternative exemplary handleconstructed in accordance with the principles of the present disclosure.

FIG. 13 is a graph illustrating a control loop of the catheter system.

FIG. 14 is a distributivity plot diagram illustrating direct targetingof energy emission in accordance with the principles of the presentdisclosure.

FIG. 15 illustrates an alternative exemplary catheter system having arotatable torque shaft constructed in accordance with the principles ofthe present disclosure.

FIG. 16 illustrates an alternative exemplary catheter system havingimaging transducers in accordance with the principles of the presentdisclosure.

FIG. 17A illustrates an alternative exemplary imaging transducer havinga shield constructed in accordance with the principles of the presentdisclosure.

FIG. 17B illustrates energy emission of the imaging transducer of FIG.17A within a patient.

FIG. 18 illustrates an alternative exemplary catheter system havingpacing electrodes in accordance with the principles of the presentdisclosure.

FIG. 19A illustrates an exemplary transducer constructed in accordancewith the principles of the present disclosure.

FIG. 19B illustrates another exemplary transducer constructed inaccordance with the principles of the present disclosure.

FIG. 19C illustrates another exemplary transducer constructed inaccordance with the principles of the present disclosure.

FIG. 19D illustrates an exemplary transducer connection implementation.

FIG. 19E illustrates another exemplary transducer constructed inaccordance with the principles of the present disclosure.

FIGS. 20A to 20D illustrate various outer surface shapes of exemplarytransducers.

FIG. 21A illustrates an exemplary lens constructed in accordance withthe principles of the present disclosure.

FIG. 21B schematically illustrates energy rays emanating from the lensof FIG. 21A to longitudinally focus and concentrate energy.

FIG. 21C illustrates a portion of an energy application shape.

FIG. 21D illustrates an exemplary transducer assembly constructed inaccordance with the principles of the present disclosure.

FIG. 22A illustrates an exemplary anchor in a collapsed delivery stateconstructed in accordance with the principles of the present disclosure.

FIG. 22B illustrates the anchor of FIG. 22A in a deployed state.

FIG. 22C illustrates another exemplary anchor in a collapsed deliverystate constructed in accordance with the principles of the presentdisclosure.

FIG. 22D illustrates the anchor of FIG. 22C in a deployed state.

FIGS. 23A and 23B illustrate an exemplary transducer assemblyconstructed in accordance with the principles of the present disclosure.

FIGS. 23C to 23E illustrate an exemplary method of rotating an anchorbetween ablations.

FIG. 24A schematically illustrates an exemplary catheter comprising ahandle and an elongate shaft constructed in accordance with theprinciples of the present disclosure.

FIG. 24B schematically illustrates another exemplary catheter comprisinga handle and an elongate shaft constructed in accordance with theprinciples of the present disclosure.

FIG. 25A illustrates another exemplary anchor in a collapsed deliverystate constructed in accordance with the principles of the presentdisclosure.

FIG. 25B illustrates the anchor of FIG. 25A in a deployed state.

FIG. 26A illustrates another exemplary anchor in a collapsed deliverystate constructed in accordance with the principles of the presentdisclosure.

FIG. 26B illustrates the anchor of FIG. 26A in a deployed state.

FIG. 27A illustrates another exemplary anchor in a collapsed deliverystate constructed in accordance with the principles of the presentdisclosure.

FIG. 27B illustrates the anchor of FIG. 27A in a deployed state.

FIG. 27C is a top view of an exemplary petal configuration for theanchor of FIG. 27A.

FIG. 27D is a side view of the petal configuration of FIG. 27C.

FIG. 28A illustrates another exemplary anchor in a collapsed deliverystate constructed in accordance with the principles of the presentdisclosure.

FIG. 28B illustrates the anchor of FIG. 28A in a deployed state.

FIG. 28C illustrates another exemplary anchor in a collapsed deliverystate constructed in accordance with the principles of the presentdisclosure.

FIG. 28D illustrates the anchor of FIG. 28C in a deployed state.

FIG. 29A illustrates another exemplary anchor in a collapsed deliverystate constructed in accordance with the principles of the presentdisclosure.

FIG. 29B illustrates the anchor of FIG. 29A in a deployed state.

FIG. 30A illustrates another exemplary anchor in a collapsed deliverystate constructed in accordance with the principles of the presentdisclosure.

FIG. 30B illustrates the anchor of FIG. 30A in a deployed state.

FIG. 31A illustrates another exemplary anchor in a collapsed deliverystate constructed in accordance with the principles of the presentdisclosure.

FIG. 31B illustrates the anchor of FIG. 31A in a deployed state.

FIG. 32A illustrates another exemplary anchor in a collapsed deliverystate constructed in accordance with the principles of the presentdisclosure.

FIG. 32B illustrates the anchor of FIG. 32A in a deployed state.

FIG. 33A illustrates an exemplary anchor in a collapsed delivery stateconstructed in accordance with the principles of the present disclosure.

FIG. 33B illustrates the anchor of FIG. 33A in a deployed state.

FIGS. 33C and 33D illustrate various views of an exemplary loop wire.

FIG. 34A illustrates an exemplary catheter in a vessel that is notproperly anchored.

FIG. 34B illustrates an exemplary catheter in which the stiffness of ashaft can be effectively negated proximate a distal portion.

FIG. 35A illustrates an exemplary retraction feature constructed inaccordance with the principles of the present disclosure.

FIG. 35B illustrates another exemplary retraction feature constructed inaccordance with the principles of the present disclosure.

FIG. 36 is a schematic diagram of an example ablation instrument inaccordance with the principles of the present disclosure.

FIG. 37A illustrates an exemplary catheter comprising a sensorconstructed in accordance with the principles of the present disclosure.

FIG. 37B is a graph depicting example temperature measurement and pulseemission during ablation.

FIG. 37C illustrates an exemplary catheter system including a secondcatheter comprising a sensor constructed in accordance with theprinciples of the present disclosure.

FIG. 37D illustrates a sensor coupled to the interior of an exemplarylens.

FIG. 37E illustrates a plurality of sensors located on an exemplaryanchor in accordance with the principles of the present disclosure.

FIGS. 38A-38B illustrate an exemplary method of inserting and navigatinga catheter to a vessel in accordance with the principles of the presentdisclosure.

FIGS. 38C-38D illustrate an exemplary method of treating tissue aroundthe right pulmonary artery in accordance with the principles of thepresent disclosure.

FIGS. 38E-38F illustrate an exemplary method of treating tissue aroundthe left pulmonary artery in accordance with the principles of thepresent disclosure.

FIGS. 38G-38I illustrate an exemplary method of treating tissue aroundthe pulmonary trunk in accordance with the principles of the presentdisclosure.

DETAILED DESCRIPTION

The interplay of the vasoconstrictive/vasodilator axis of the pulmonarycirculation is one of the key determinants of pulmonary hypertensiondisease progression and severity. The sympathetic nervous systemmediates pulmonary vasoconstriction. This may be specificallyaccomplished by the thoracic sympathetic chain and branches thereof. Thesympathetic nervous system may be important in the mediation of thehypoxia mediated vasoconstrictive response of the pulmonary arterialvasculature. Modulating or reducing the sympathetic nervous systemactivity within the pulmonary vasculature is a unique approach for thetreatment of pulmonary hypertension. Reducing, modulating, an/ornegating sympathetic tone to the pulmonary arteries reduces sympatheticmediated vasoconstriction, thereby allowing for increased pulmonaryvascular diameter and pulmonary vascular dilatation. The end effect ofreducing sympathetic tone is a reduction in pulmonary pressure andpulmonary hypertension, a possible goal of therapy.

Although this Detailed Description focuses on treatment of sympatheticnerves, nerve fibers and/or neurons, in any given embodiment, a method,device or system described herein may also or alternatively treatparasympathetic nerves, nerve fibers, and/or neurons. Therefore,descriptions herein of treating sympathetic nervous tissue should not beinterpreted as limiting.

Pulmonary Neurovascular Anatomy

The sympathetic innervation of the lung and the heart arises from thethoracolumbar spinal column, ultimately reaching the heart and lung andinnervating its vasculature. The sympathetic nervous system is part ofthe autonomic nervous system, comprising nerve fibers that leave thespinal cord in the thoracic and lumbar regions and supply viscera andblood vessels by way of a chain of sympathetic ganglia running on eachside of the spinal column which communicate with the central nervoussystem via a branch to a corresponding spinal nerve. The sympatheticnerves arising from primarily the thoracic spine (e.g., levels T1-T10with some potential contribution from the cervical spine) innervate theheart and the lungs after branching out from the thoracic sympatheticchain. The sympathetic nerves converge upon the thoracic sympatheticchain and ganglion, after which arise the post ganglionic sympatheticnerves which then innervate the heart and the lungs. These nerves oftenconverge upon various plexi or plexuses which are areas of convergenceoften of both sympathetic and parasympathetic nerve fibers. Theseplexuses then further give rise to nerve branches or continuations,which then branch and ramify onto structures within the heart and lungsor in association with the outer walls of the pulmonary arteries orarterioles for instance. Some of the key plexuses and their anatomicrelationship to the heart, lung, and pulmonary vasculature are describedherein.

The great plexuses of the sympathetic are aggregations of nerves andganglia, situated in the thoracic, abdominal, and pelvic cavities, andnamed the cardiac, celiac, and hypogastric plexuses. They include notonly sympathetic fibers derived from the ganglia, but also fibers fromthe medulla spinalis, which are conveyed through the white ramicommunicantes. From the plexuses, branches are given to the thoracic,abdominal, and pelvic viscera.

The cardiac plexus is situated at the base of the heart, and is dividedinto a superficial part, which lies in the concavity of the aortic arch,and a deep part, which is between the aortic arch and the trachea. Thesuperficial and deep parts are closely connected.

The superficial part of the cardiac plexus lies beneath the arch of theaorta, in front of the right pulmonary artery. The superficial part ofthe cardiac plexus is formed by the superior cardiac branch of the leftsympathetic and the lower superior cervical cardiac branch of the leftvagus. A small ganglion, the cardiac ganglion of Wrisberg, isoccasionally found connected with these nerves at their point ofjunction. This ganglion, when present, is situated immediately beneaththe arch of the aorta, on the right side of the ligamentum arteriosum.The superficial part of the cardiac plexus gives branches (a) to thedeep part of the plexus; (b) to the anterior coronary plexus; and (c) tothe left anterior pulmonary plexus.

The deep part of the cardiac plexus is situated in front of thebifurcation of the trachea, above the point of division of the pulmonaryartery, and behind the aortic arch. The deep part of the cardiac plexusis formed by the cardiac nerves derived from the cervical ganglia of thesympathetic and the cardiac branches of the vagus and recurrent nerves.The only cardiac nerves which do not enter into the formation of thedeep part of the cardiac plexus are the superior cardiac nerve of theleft sympathetic and the lower of the two superior cervical cardiacbranches from the left vagus, which pass to the superficial part of theplexus.

The branches from the right half of the deep part of the cardiac plexuspass, some in front of and others behind, the right pulmonary artery;the branches in front of the pulmonary artery, which are more numerousthan the branches behind, transmit a few filaments to the anteriorpulmonary plexus, and then continue onward to form part of the anteriorcoronary plexus; those behind the pulmonary artery distribute a fewfilaments to the right atrium, and then continue onward to form part ofthe posterior coronary plexus.

The left half of the deep part of the plexus is connected with thesuperficial part of the cardiac plexus, and gives filaments to the leftatrium, and to the anterior pulmonary plexus, and then continues to formthe greater part of the posterior coronary plexus.

The Posterior Coronary Plexus (plexus coronarius posterior; leftcoronary plexus) is larger than the Anterior Coronary Plexus, andaccompanies the left coronary artery. The Posterior Coronary Plexus ischiefly formed by filaments prolonged from the left half of the deeppart of the cardiac plexus, and by a few from the right half. ThePosterior Coronary Plexus gives branches to the left atrium andventricle.

The Anterior Coronary Plexus (plexus coronarius anterior; right coronaryplexus) is formed partly from the superficial and partly from the deepparts of the cardiac plexus. The Anterior Coronary Plexus accompaniesthe right coronary artery. The Anterior Coronary Plexus gives branchesto the right atrium and ventricle.

The pulmonary plexuses are the sites of convergence of autonomic fiberswhich supply the lung. The pulmonary plexuses are in continuity with thecardiac plexuses, which lie superiorly, and the oesophageal plexuses,which lie posterosuperiorly.

The pulmonary plexuses are sited anterior and posterior relative to eachlung root. The pulmonary plexuses are in close proximity to thepulmonary arteries and, as they branch laterally, the pulmonary plexusesramify their nerve fibers in association with the outer walls ofdiverging pulmonary arteries and arterioles.

The passage of fibers from the cardiac plexus is inferiorly, anterior tothe trachea and posterior to the aortic arch. The pulmonary plexus alsoreceives autonomic fibers directly from other sources. The pulmonaryplexus receives parasympathetic fibers directly from the right vagusnerve, which descends posteroinferiorly on the trachea and dividesposterior to the trachea to give pulmonary and oesophageal plexuses;pulmonary plexus passes anteriorly to root of the lung. The pulmonaryplexus also receives parasympathetic fibers directly from the left vagusnerve, which descends anteriorly to arch of aorta, gives off recurrentlaryngeal branch, and then fibers diverge anteriorly to supply the leftpulmonary arterial plexus. The pulmonary plexus receives sympatheticfibers directly from rami of the superior four thoracic ganglia, whichpass anteriorly around the posterior thoracic cage to merge on thelateral walls of the esophagus. The rami supply nerve fibers to thepulmonary plexus from the region dorsal to the tracheal bifurcation.

The recurrent cardiac nerve and sometimes the craniovagal cardiac nervescan carry the main innervation of the pulmonary bifurcation and adjacentparts of the main pulmonary artery and its right and left branches. Therecurrent cardiac nerve is a moderately large nerve, arising from theright recurrent laryngeal nerve as it loops around the right subclavianartery. The recurrent cardiac nerve usually receives a contribution ofvarying size from the vagal, parasympathetic trunk, and another from thestellate ganglion. The nerve passes dorsally to the anterior vena cava,laterally to the brachiocephalic artery and arch of the aorta, to thepulmonary bifurcation, to where it divides into anterolateral andposterolateral branches. The anterolateral branch tends to be smaller.The branches then tend to fan out over the anterior and posterioraspects of the main pulmonary artery and communicate with plexi aroundthe right and left pulmonary arteries and the pretracheal plexus. Somefibers continue to the heart and the coronary plexi. During its course,it communicates freely with the cranio-vagal cardiac nerves.

The right vagal cardiac nerves arise from the right vagus trunk caudalto the origin of the right recurrent laryngeal nerve. They fall into twogroups, the cranial and caudal vagal cardiac nerves. These vary in size,number, and course. Including some of the smaller divisions, he rightvagal cardiac nerves supply branches or twigs to the right pulmonaryartery plexus, the antero and posterolateral branches of the rightrecurrent cardiac nerve at the pulmonary bifurcation, and to the plexusformed by the ventral branch of the vagus, anterior to the pulmonaryroot, and then terminate in the atrial wall. Small twigs or branches,variable in size and position and sometimes absent, are supplied to thepre-tracheal plexus and the plexus around the right and left pulmonaryartery by the right stellate cardiac nerves, the venteromedial cervicalcardiac nerve, the left recurrent laryngeal nerve, and the ventralbranch of the left vagal trunk. Other twigs or branches are suppliedfrom a diffuse plexiform network of fibers form the ventrolateralcardiac nerve and the left stellate cardiac nerve.

One of these nerves that is of interest is the recurrent cardiac nerve,especially the right recurrent cardiac nerve, as it can containpre-ganglionic, afferent and sympathetic post-ganglionic fibers amongothers. The recurrent cardiac nerve is a branch of the right recurrentlaryngeal nerve, the nerve of visceral arch. It is therefore ofconsiderable interest that the main nerve supply to the pulmonarybifurcation sensory area, part of the visceral arch, is derived from therecurrent laryngeal nerve, the nerve of visceral arch. As the mostcephalic part of the pulmonary artery is formed from the posterior andright lateral parts of the bulbus cordis, this vessel is predominantlysupplied from the right visceral nerve.

More specifically, the pulmonary artery bifurcation and adjacentportions of the right and left pulmonary arteries receive a very richinnervation. On the right side, the most constant nerve trunk to thebifurcation is the right recurrent cardiac nerve. The fibers arise fromthe vagus or the recurrent laryngeal nerve as it loops around thesubclavian artery immediately cuadad to its origin from thebrachiocephalic trunk. The nerve proceeds medially and caudally passingdorsal to the superior vena cava and lateral to the origin of thebrachiocephalic trunk. The fibers ramify at the bifurcation by dividinginto antero-lateral and postero-lateral branches which communicate withthe fibers from the pulmonary plexuses. During its course itcommunicates with one or more right vagal cardiac nerves, usually ofvery small size, and branches from the stellate ganglia or ansasubclavia. These latter branches are thought to contribute the efferentcomponent. Minor variation in the mode of origin from the recurrentlaryngeal nerve (RLN) were noted. In some cases, the nerve can arise asa separate trunk from the loop of the RLN and can be joined by acardiosympathetic branch from the adjacent stellate ganglion. Therecurrent cardiac nerve can rarely arise from the angle of origin of theRLN as well. In some cases, the major portion of the nerve can arisefrom the vagus as the vagal cardiac nerve, also receiving a smallfilament from the RLN.

The contribution to the innervation of the pulmonary artery from theleft side is similar to that of the right, but also receives in somecases invariably a small, direct contribution from the vagus in the formof the ventro-medial-cervical cardiac nerve. This nerve arises from thevagus by a variable number of roots, usually two, and proceeds caudallypassing over the aortic arch to ramify over the ligamentum arteriosum,pulmonary bifurcation and left pulmonary artery. The superior craniovagal root usually receives a direct branch from the left stellateganglion. The bifurcation and left pulmonary artery receive a smallinconstant branch from the RLN as it passes under the aortic arch. Insome cases, the descending branches arise from the ascending portion ofthe RLN to terminate around the bifurcation.

The musculature of the pulmonary artery receives a right sidedinnervation of predominantly vasoconstrictor adrenergic sympatheticfibers, but little to no motor innervation from the parasympathetics orvagus nerve. The fibers synapse mainly in the stellate, but also in theupper thoracic and sympathetic ganglia. A large concentration of nerveendings are found at the bifurcation of the pulmonary artery, as well asin parts of the adjacent pulmonary artery and its right and left mainbranches.

Beyond the main pulmonary artery, right main and left main pulmonaryarteries, the innervation of the further branches of the lung followsthe arterial anatomy, with the nerves coursing along the arteries,typically following a peri-adventitial location or coursing along theadventitia. A rich innervation exists in pulmonary arteries furtherdistal and to pulmonary arterioles as small as 30 microns in diameter orsmaller. This innervation includes both parasympathetic and sympatheticinnervation, with the lungs considered to have a rich sympathetic nervesupply.

Thoracic sympathectomy is a surgical procedure that currently exists andis utilized in the treatment of a different disease process, namelyhyperhidrosis syndrome (excessive sweating). Extensive research on thissurgical procedure has shown it to be safe and efficacious.Physiological studies of patients undergoing thoracic sympathectomy haveshown mild changes in pulmonary function and mild increases in airwayresistance, small decreases in heart rate however preserved leftventricular function and ejection fractions, and also preserved exercisetolerance. Data from T2-T3 video assisted thoracoscopic sympathectomypatients have shown that sympathectomy results in severing theipsilateral hypoxia mediated vasoconstrictive pathway to the pulmonaryvasculature by demonstrating a drop in arterial oxygen saturation duringcontralateral selective lung ventilation both prior and subsequent tosympathectomy. This implies ipsilateral pulmonary vascular dilatationand reduction in pulmonary pressure. Although thoracic sympathectomy hasbeen used for treating hyperhidrosis, it has not been described, priorto the provisional patent application from which this application claimspriority, for treating pulmonary hypertension. More generally,decreasing activity of one or more sympathetic nerves or neurons toreduce pulmonary vascular resistance and/or to ameliorate pulmonaryhypertension has not been described previously.

Treatment Devices

Referring now to FIGS. 1A and 1B, an exemplary catheter system forreducing neural activity of nerves around a blood vessel, e.g., apulmonary artery, of a patient is provided. For example, neural activitymay be reduced by inactivating the nerves. Catheter system 100 mayinclude proximal region 102, distal region 104, and elongated shaft 101extending between proximal region 102 and distal region 104. Cathetersystem 100 further may include anchor 200 and transducer 114 disposed atdistal region 104, and handle 300 disposed at proximal region 102.Handle 300 may be operatively coupled to anchor 200 and transducer 114,e.g., through elongated shaft 101, such that handle 300 may be actuatedby a user to actuate anchor 200 and transducer 114. For example, handle300 may be used to guide distal region 104 to a target location within ablood vessel, and then actuated to deploy anchor 200 within the bloodvessel to thereby centralize transducer 114 within the blood vessel.Handle 300 further may be actuated to cause transducer 114 to emitenergy to the blood vessel to reduce neural activity of nervessurrounding the blood vessel. Handle 300 also may be used to repositiondistal region 104 to another portion of the blood vessel, e.g., from theright pulmonary artery to the left pulmonary artery and/or the mainpulmonary artery, such that neural activity of the nerves surroundingthe other portion of the blood vessel also may be reduced via transducer114. Upon completion of the ablation therapy, catheter system 100 may beremoved from the patient.

Referring now to FIG. 1B, elongated shaft 101 is described. As shown inFIG. 1B, elongated shaft 101 may include a plurality of catheters, e.g.,inner catheter 110, transducer shaft 112, outer catheter 116, sheath118, and separation sleeve 120. For example, inner catheter 110 may bethe innermost catheter of elongated shaft 101, and may have a proximalregion operatively coupled to handle 300, and a distal region havingatraumatic tip 111. Inner catheter 110 may have a lumen extendingtherethrough, including through tip 111, such that the lumen is sizedand shaped to receive a guidewire therethrough. For example, theguidewire lumen may be between 0.050″ and 0.080″ along the length ofinner catheter 110, and may guide a, e.g., 0.035″ guidewire or smaller.Accordingly, a proximal end of a guidewire may be fed through the lumenof tip 111, such that catheter system 100 may be advanced over theguidewire to position distal region 102 within the target location inthe blood vessel, as described in further detail below. Inner catheter110 may be actuatable via handle 300 to move inner catheter 110translationally relative to handle 300.

Catheter system 100 may include a transducer assembly, which includestransducer shaft 112 having a proximal region operatively coupled tohandle 300, and transducer 114 disposed at the distal region oftransducer shaft 112. Transducer shaft 112 may have a cylindrical shape,and a lumen extending therethrough, such that the lumen is sized andshaped to slidably receive inner catheter 110 therein. Accordingly,inner catheter 110 may move relative to transducer shaft 112. Transducer114 may be configured to effect neuromodulation, e.g., via ablation,denervation, which may or may not be reversible, stimulation, etc. Forexample, transducer 114 may convert electrical input into an acousticbeam that will be absorbed by the target tissue to induce heating of thenerves surrounding/innervating the blood vessel to thereby reduce neuralactivity of the nerves. For example, transducer 114 may be arcuateultrasound transducer having a piezoelectric element for emittingultrasonic energy, e.g., focused or unfocused ultrasound. Alternatively,the transducers described herein may be configured to emit radiofrequency (RF) energy, microwave energy, cryo energy, thermal energy,electrical energy, infrared energy, laser energy, phototherapy, plasmaenergy, ionizing energy, mechanical energy, chemical energy,combinations thereof, and the like.

Outer catheter 116 may have a proximal region operatively coupled tohandle 300, and a lumen extending therethrough, such that the lumen issized and shaped to receive transducer shaft 112 therein. A distalregion of outer catheter 116 may be coupled to transducer 114 andtransducer shaft 112. For example, the distal region of outer catheter116 may be sealed with the distal region of transducer shaft 112 tocreate a fluidically sealed cavity therebetween. Moreover, at least onecable may be disposed in the fluidically sealed cavity and electricallycoupled to transducer 114 to provide electrical energy to transducer114. Outer catheter 116 may be actuatable via handle 300 to move outercatheter 116 translationally relative to handle 300. Accordingly, outercatheter 116 may move relative to inner catheter 110.

As shown in FIG. 1B, a proximal end of anchor 200 may be coupled toouter catheter 116, and a distal end of anchor 200 may be coupled toinner catheter 110. Accordingly, relative movement between innercatheter 110 and outer catheter 116, e.g., via a push-pull mechanism,may cause anchor 200 to transition between a collapsed delivery stateand an expanded deployed state. For example, moving inner catheter 110distally relative to outer catheter 116 may cause anchor 200 to collapsetoward the longitudinal axis of elongated shaft 101, and moving innercatheter 110 proximally relative to outer catheter 116 may cause anchorto expand outwardly from the longitudinal axis of elongated shaft 101.In the expanded deployed state, anchor 200 may contact the inner wall ofthe blood vessel to centralize transducer 114 within the blood vessel.Accordingly, in the expanded deployed state, anchor 200 may have aradial force that is greater than a stiffness force of inner catheter110, transducer shaft 112, outer catheter 116, and distal region 118 bof sheath 118. Anchor 200 may be configured to preserve blood flowthrough the vessel in the expanded deployed state.

Sheath 118 may have proximal region 118 a operatively coupled to handle300, distal region 118 b, and a lumen extending therethrough, such thatthe lumen is sized and shaped to slidably receive outer catheter 116 andanchor 200 in its collapsed delivery state therein. Proximal region 118a may have a longer and thinner profile than distal region 118 b, toreduce the forces of elongated shaft 101 against the patient's anatomy.Reducing this force reduces the amount of force required by anchor 200to centralize transducer 114. However, this reduction of force ofproximal region 118 a must be balanced against the stiffness of distalregion 118 b of sheath 118 required to cover anchor 200. For example,distal region 118 b should be stiff enough to slide over anchor 200without compression nor buckling. This feature may be addressed thoughthe appropriate material selection, the appropriate braid (wire profile& PPI), but also through the preconditioning of sheath 118 before itsintegration to catheter system 100.

Distal region 118 b of sheath 118 may have a stiffness sufficient tofacilitate transitioning of anchor 200 from the expanded deployed stateto the collapsed delivery state upon movement of distal region 118 bdistally relative to anchor 200 without buckling distal region 118 b.Accordingly, distal region 118 b may have a stiffness that is greaterthan the stiffness of proximal region 118 a of sheath 118. For example,as shown in FIG. 1B, distal region 118 b may have an outer diameter thatis larger than the outer diameter of proximal region 118 a, e.g., distalregion 118 b may have a cross-sectional area that is larger than thecross-sectional area of proximal region 118 a. Accordingly, proximalregion 118 a may have more flexibility to facilitate maneuvering ofcatheter system 100 through the patient's vasculature. In addition,sheath 118 may be moved distally relative to inner catheter 110 untilanchor 200 is disposed within the lumen of sheath 118 in its collapseddelivery state, e.g., within distal region 118 b, and the distal end ofdistal region 118 b engages with a proximal end of tip 111, therebyforming a seal, such that catheter system 100 is in a deliveryconfiguration. Accordingly, distal region 118 b may have an outerdiameter that is substantially equal to the outer diameter of theproximal end of tip 111, to provide a smooth and/or continuous outersurface in the delivery configuration.

Separation sleeve 120 may be fixedly coupled to handle 300, and may havea lumen extending therethrough, such that the lumen is sized and shapedto slidably receive at least proximal region 118 a of sheath 118therein. Accordingly, sheath 118 may move relative to separation sleeve120, e.g., when sheath 118 is actuated via handle 300. Separation sleeve120 may extend along at least a portion of the proximal region ofelongated shaft 101. Preferably, separation sleeve 120 does not extendalong the entire length of elongate shaft 101 so as to provide a smallerfootprint and more flexibility of catheter system 100.

Separation sleeve 120 may be configured to permit handle 300 to be fixedrelative to the patient. For example, catheter system 100 further mayinclude an introducer, which may be inserted into the patient at anentry site and fixed relative to the patient. The introducer may have alumen extending therethrough, such that the lumen is sized and shaped toslidably receive elongated shaft 101 therethrough, e.g., in the deliveryconfiguration. For example, tip 111 may be advanced over the guidewire,through the lumen of the introducer, such that elongated shaft 101 isdelivered through the patient's vasculature via the introducer. Duringunsheathing and resheathing of anchor 200 and transducer 114 viaproximal and distal translational movement of sheath 118 relative toanchor 200 and transducer 114, it may be desirable to fix the positionof handle 300 relative to the patient, such that inadvertent movement oftransducer 114 and/or anchor 200 may be avoided as sheath 118 is movedrelative to handle 300. Accordingly, separation sleeve 120 may befixedly coupled to the introducer, which is fixedly coupled to thepatient. For example, the transducer may have a valve disposed withinits lumen, such that upon actuation thereof, the valve is actuatedagainst separation sleeve 120 when separation sleeve 120 is disposedwithin the lumen of the introducer. By fixing the position of separationsleeve 120, which is fixedly coupled to handle 300, relative to theintroducer, which is fixedly coupled to the patient, handle 300, andaccordingly transducer 114 and/or anchor 200, will also be fixedrelative to the patient, and accordingly to the blood vessel, such thatsheath 118 may be moved proximally and distally relative to transducer114 and/or anchor 200 while transducer 114 and/or anchor 200 remainunmoved relative to the blood vessel.

Elongated shaft 101 may include additional lumens. For example, anoptional lumen may be used to track catheter system 100 over aguidewire. In addition, an optional lumen may provide a passage forconductor wires, e.g., cable 600, between transducer 114 and a signalgenerating system. Additionally, an optional lumen may provide passagefor a conductor wire between a sensor and a receiving station. Moreover,an optional lumen may be provided to deliver coolant to transducer 114during sonication/ablation. For example, cold saline may be deliveredthrough the lumen, e.g., via a pressure bag or a dedicated infusionpump, and through an outlet located close to the transducer to cool downthe transducer and the surrounding blood that is heated by the Jouleeffect of the transducer.

Referring now to FIGS. 2A to 2C, distal region 104 of catheter system100 is described. Distal region 104 is sized and shaped to be disposedwithin a blood vessel, e.g., the right, left, and/or main pulmonaryarteries. As shown in FIGS. 2A and 2B, proximal end 202 of anchor 200may be coupled to outer catheter 116 at an axial position proximal totransducer 114, and distal end 204 of anchor 200 may be coupled to innercatheter 110 at an axial position distal to transducer 114, such thattransducer 114 is disposed within anchor 200. Anchor 200 may be formedof shape memory material, e.g., Nitinol, chromium cobalt, MP35N, 35NPT,Elgiloy, etc.). As shown in FIGS. 2A and 2B, anchor 200 may be formed ofa plurality of struts extending from proximal end 202 to distal end 204of anchor 200. The plurality of struts may be cut (e.g., laser cut) froma hypotube or sheet. For example, the plurality of struts may include aplurality of connections forming diamond-shaped struts, which form acage in the expanded deployed state, and prevent grouping of the strutswhile pushing against the vessel wall. Accordingly, in the expandeddeployed state, anchor 200 may centralize transducer 114 within theblood vessel while not occluding the blood vessel, thereby preservingblood flow through the blood vessel.

Anchor 200 is configured to centralize transducer 114 in both a straightor curved blood vessel, which may help ensure that tissue all around thevessel is treated. In a curved vessel, the radial force exerted byanchor 200 on the inner wall of the vessel must be greater than theforce inherent from the stiffness of elongated shaft 101 to centralizetransducer 114 within the curved vessel. The radial force of anchor 200is derived from the material composition of anchor 200, e.g., Nitinol,and from the longitudinal compression of anchor 200. Anchor 200 may havea rectangular profile to avoid the plurality of struts slipping over theinner wall of the blood vessel.

As described above, relative movement between inner catheter 110 andouter catheter 116 may cause anchor 200 to transition between acollapsed delivery state and an expanded deployed state. Preferably,outer catheter 116 is fixed relative to handle 300, and inner catheter110 may be actuated via handle 300 to move proximally and distallyrelative to outer catheter 116 to expand and collapse anchor 200, asdescribed in further detail below with regard to FIGS. 4B and 4C.Alternatively, inner catheter 110 is fixed relative to handle 300, andouter catheter 116 may be actuated via handle 300 to move proximally anddistally relative to outer catheter 116 to expand and collapse anchor200. In this configuration, outer catheter 116 may be retractedproximally relative to sheath 118 and inner catheter 110 to thereby pulland collapse anchor 200 into sheath 118, e.g., by pulling the proximalend of anchor 200 into sheath 118. In another alternative embodiment,both inner catheter 110 and outer catheter 116 may be actuated viahandle 300, e.g., via a single actuator operatively coupled to bothinner catheter 110 and outer catheter 116, such that actuation of thesingle actuator causes inner catheter 110 and outer catheter 116 to movetoward and away from each other in equal and opposite directions.

In yet another alternative embodiment, anchor 200 may be formed of aself-expanding material, such that anchor 200 is biased toward theexpanded deployed state. Moreover, the distal end of anchor 200 may becoupled to inner catheter 110 via a ring slidably disposed on innercatheter 110, such that the distal end of anchor 200 is slidably coupledto inner catheter 110. Accordingly, upon retraction of sheath 118 toexpose anchor 200 within the blood vessel, anchor 200 may self-expand asthe ring slides across inner catheter 110 to permit the distal end ofanchor 200 to move proximally toward the proximal end of anchor 200. Inthis configuration, resheathing of anchor 200 via sheath 118 requiresless forces because the distal end of anchor 200 is not fixed to innercatheter 110 and sheath 118 does not have to pull the tip/inner materialto resheath anchor 200. Additionally, it would allow the use of moreflexible material and reduce the forces over the patient anatomy andguide catheter system 100 more easily in small anatomies.

Alternatively, anchor 200 may be formed of a self-expanding material,such that anchor 200 is biased toward the collapsed delivery state. Inthis configuration, more longitudinal force would be required to moveinner catheter 110 and outer catheter 116 toward each other to expandanchor 200; however, distal region 118 b would require less stiffness,and therefore may be more flexible as distal region 118 b would not needas much stiffness to collapse and cover anchor 200. Moreover, anchor 200would have less to compete against the stiffness of the elongated shaft101 to induce centralization of transducer 114. Moreover, the reductionof the profile of the catheter assembly in the section proximal totransducer 114 may prevent or otherwise limit heart straining, and alsomay limit valve regurgitation while transducer 114 is located in thepulmonary artery, which would be beneficial for a pulmonary hypertensionpatient as they may only accommodate limited time of heart strainingduring catheter delivery.

In the expanded deployed state, anchor 200 may have a cross-sectionalarea that corresponds with the cross-sectional area of the blood vessel,such that anchor 200 applies sufficient force to the inner wall of theblood vessel to secure and centralize transducer 114 within the bloodvessel. Preferably, anchor 200 does not distend the blood vessel in theexpanded deployed state. Accordingly, relative movement between innercatheter 110 and outer catheter 116 may be selectively actuated viahandle 300 to expand anchor 200 to a predetermined size that correspondswith the target vessel.

As further shown in FIGS. 2A and 2B, atraumatic tip 111 may have atapered profile. For example, the cross-sectional area of tip 111 maydecrease from the proximal end of tip 111 toward the distal end of tip111. The taper profile is gradual to guide distal region 118 b of sheath118 during resheathing of anchor 200 in both a straight line and curvedconfiguration, e.g., in a curved portion of the pulmonary artery.Moreover, the taper ensures there is no gap between tip 111 and distalregion 118 b in the resheathed delivery configuration to preventpinching of tissue during resheathing and navigation through thepatient's vasculature. Tip 111 may be made of a soft material with athickness selected to prevent damaging the IVC or SVC, right atrium,right ventricle, valves and pulmonary artery during catheter navigation.

As shown in FIG. 2C, sheath 118 may be a flexible coil, e.g., lasercutstainless steel, to provide sufficient flexibility while limitingcompressibility of sheath 118, e.g., to prevent buckling of distalregion 118 b as sheath 118 is advanced distally relative to anchor 200to facilitate collapsing of anchor 200 into the lumen of sheath 118.This is beneficial as the femoral access in human constrains thecatheter into a ‘S’ shape, and the smaller the anatomy is, the smallerthe bend radii of the two slopes of the ‘S’ are, leading to maximizationof the forces between the catheter and the RA (Right Atrium) or RV(Right Ventricle). These forces may lead to the heart straining which isnot favorable for the treatment of a pulmonary hypertension patient. Tolimit these forces, the stiffness of the catheter may be reduced, whichis driven by the stiffness of its stack of shafts. The stiffness of theshaft depends on several properties, such as the raw material or thewall thickness. Moreover, elongated shaft 101 further needs to supportthe forces of anchor 200 to either collapse or compress anchor 200.Thus, elongated shaft 101 must have limited compressibility, e.g.,capped to 2 mm over the course of up to 2 meters of tubing. Accordingly,forming sheath 118, inner catheter 110, and/or outer catheter 116 of aflexible coil, e.g., lasercut stainless steel, may provide sufficientflexibility while limiting compressibility. Alternatively, elongatedshaft 101 may be preconditioned in a fixture in a heated environmentthat forces that compression of elongated shaft 101 before integrationin catheter system 100. Accordingly, elongated shaft 101 also may bepreconditioned against its elongation.

Referring now to FIG. 3 , handle 300 is described. Handle 300 mayinclude frame 302 and one or more actuators, e.g., knob 304 and knob306, and/or a thumb wheel or slider. Knob 304 may be operatively coupledto at least one of inner catheter 110 or outer catheter 116, and may beconfigured to be rotated to cause relative movement between innercatheter 110 and outer catheter 116, to thereby transition anchor 200between the collapsed delivery state and the expanded deployed state.For example, rotating knob 304 in a first direction may cause innercatheter 110 and outer catheter to move toward each other, therebycausing anchor 200 to deploy to the expanded deployed state, androtating knob 304 in a second direction opposite to the first directionmay cause inner catheter 110 and outer catheter 116 to move away fromeach other, thereby causing anchor 200 to collapse to the collapseddelivery state. As the user actuates knob 304, the user may be able tofeel when the struts of anchor 200 contact the vessel wall and may stopexpanding anchor 200 at the appropriate deployed state.

Knob 304 may be operatively coupled to only inner catheter 110, suchthat rotation of knob 304 causes inner catheter 110 to move relative toouter catheter 116. Alternatively, handle 300 may include separateactuators operatively coupled to each of inner catheter 110 and outercatheter 116, such that inner catheter 110 and outer catheter 116 may beindependently actuatable.

Knob 306 may be operatively coupled to sheath 118, and may be configuredto be rotated to cause movement of sheath 118 relative to handle 300 andthe other components of catheter system 100, e.g., anchor 200 andtransducer 114, to thereby unsheathe anchor 200 and transducer 114 orresheath anchor 200 and transducer 114. For example, rotating knob 306in a first direction may cause sheath to retract proximally relative toanchor 200 and transducer 114 to thereby expose anchor 200 andtransducer 114, and rotating knob 306 in a second direction opposite tothe first direction may cause sheath 118 to move distally relative toanchor 200 and transducer 114 to thereby cover anchor 200 and transducer114. Knobs 304 and 306 may be selectively actuated together tofacilitate collapsing of anchor 200 into the lumen of sheath 118. Forexample, knob 304 may be rotated to cause inner catheter 110 and outercatheter 116 to move away from each other, thereby causing anchor 200 tocollapse to the collapsed delivery state, while knob 306 issimultaneously rotated to move sheath distally relative to anchor 200 tothereby push against anchor 200 and facilitate collapsing of anchor 200into the lumen of sheath 118.

Referring now to FIGS. 4A to 4E, the internal components of handle 300are provided. FIG. 4A is a cross-sectional view of catheter system 100,and particularly handle 300. FIG. 4B is a close up view of circle 4B ofFIG. 4A, FIG. 4C is a close up view of circle 4C of FIG. 4A, FIG. 4D isa close up view of circle 4D of FIG. 4A, and FIG. 4E is a close up viewof circle 4E of FIG. 4A. As shown in FIG. 4B, handle 300 may includeinner catheter hub 308 operatively coupled to a proximal region of innercatheter 308. Inner catheter hub 308 may be operatively coupled to knob304, e.g., via protrusion 309 of hub 308 and groove 305 of knob 304,such that as knob 304 is rotated, rotation of groove 305 causesprotrusion 309 to move along groove 305, which causes translationalmovement of hub 318, and accordingly inner catheter 110.

As shown in FIG. 4C, handle 300 may include outer catheter hub 310operatively coupled to a proximal region of outer catheter 116. Hub 310may be configured to fixedly coupled outer catheter 116 to handle 300,and may include hub cap 314 and sealing ring 316, e.g., an O-ring, forpermitting inner catheter 110 to pass therethrough while sealing thelumen of outer catheter 116.

As shown in FIG. 4D, handle 300 may include sheath hub 318 operativelycoupled to a proximal region of sheath 118. Sheath hub 318 may beoperatively coupled to knob 306, e.g., via protrusion 319 of hub 318 andgroove 307 of knob 306, such that as knob 306 is rotated, rotation ofgroove 307 causes protrusion 319 to move along groove 307, which causestranslational movement of hub 318, and accordingly sheath 118.

As shown in FIG. 4E, handle 300 may include separation sleeve hub 324operatively coupled to a proximal region of separation sleeve 120. Hub324 may be configured to fixedly coupled separation sleeve 120 to handle300, and may include hub cap 326 and sealing ring 328, e.g., an O-ring,for permitting sheath 128 to pass therethrough while sealing the lumenof separation sleeve 120.

Referring now to FIGS. 5A and 5B, the deployment and deliveryconfigurations of catheter system 100 are provided. FIG. 5A illustratescatheter system 100 in a delivery configuration. As shown in FIG. 5A, inthe delivery configuration, sheath 118 is advanced distally such thatthe distal end of distal region 118 b of sheath 118 engages with theproximal end of tip 111, and anchor 200 is disposed within the lumen ofdistal region 118 b in its collapsed delivery state. Distal region 104of catheter system 100 may be advanced to the target location within theblood vessel in the delivery configuration, e.g., through the introducerand over the guidewire.

When distal region 104 is in the target location within the bloodvessel, anchor 200 may be ready to be deployed to centralize transducer114 within the blood vessel, such that transducer 114 may emit energy toprovide an ablation therapy. As described above, the introducer may beactuated to fix the position of handle 300 relative to the patient viaseparation sleeve 120 when transducer 114 is in the target locationwithin the blood vessel. As shown in FIG. 5B, sheath 118 may beretracted proximally relative to anchor 200 and transducer 114, e.g., byrotating knob 306, while anchor 200 and transducer 114 remain stationaryrelative to the target location within the blood vessel, to therebyexpose anchor 200 within the blood vessel. Upon exposure from sheath118, anchor 200 may remain in a partially or fully collapsed deliverystate. For example, anchor 200 may be biased toward the expandeddeployed state to facilitate deployment of anchor 200 by the relativemovement of inner catheter 110 and outer catheter 116. Accordingly, whenanchor 200 is exposed from sheath 118, at least a portion of anchor 200may begin to self-expand toward the expanded deployed state. Knob 304may then be rotated to translationally move inner catheter 110proximally relative to outer catheter 116, to thereby cause anchor 200,which is coupled to both inner catheter 110 and outer catheter 116, todeploy to the expanded deployed state, as shown in FIG. 5B.

With anchor 200 properly deployed within the blood vessel, transducer114 will be centralized within the blood vessel, and may be actuated toemit energy to the blood vessel to reduce neural activity of the nervessurrounding the blood vessel. When the ablation therapy is complete inthe target location within the blood vessel, to reposition transducer114 to another target location within the blood vessel, e.g., from theleft pulmonary artery to the right pulmonary artery and/or the mainpulmonary artery, knob 304 may be rotated in the opposite direction totranslationally move inner catheter 110 distally relative to outercatheter 116, to thereby cause anchor 200 to transition to the collapseddelivery state. In addition, knob 306 may be simultaneously rotated inthe opposite direction to transitionally move sheath 118 distallyrelative to anchor 200, such that the distal end of distal region 118 bof sheath 118 engages with anchor 200 and pushes against anchor 200 tofacilitate collapsing of anchor 200 to its collapsed delivery state,until anchor 200 is disposed within the lumen of distal region 118 b inthe collapsed delivery state.

Alternatively, knob 306 may be rotated to transitionally move sheath 118distally relative to anchor 200 after inner catheter 110 has been moveddistally relative to outer catheter 116, such that anchor 200 is atleast partially in its collapsed delivery state. Accordingly, as distalregion 118 b of sheath 118 moves over anchor 200, anchor 200 will bereceived within the lumen of distal region 118 b in the collapseddelivery state. Sheath 118 may be moved until the distal end of distalregion 118 b engages with tip 111 in the delivery configuration. Distalregion 104 of catheter system 100 may then be repositioned to positiontransducer 114 in the other target location within the blood vessel,such that anchor 200 may be redeployed and transducer 114 may provideadditional ablation therapies. Once all of the ablation therapies arecomplete, catheter system 100 may be returned to the deliveryconfiguration, and removed from the patient.

Referring now to FIGS. 6A to 6D, the connection mechanism of outercatheter 116 and the transducer assembly is provided. As shown in FIGS.6A to 6C, transducer shaft 112 may be coupled to transducer 114. Adistal region of transducer shaft 112, proximal to transducer 114, mayinclude one or more barb portions, e.g., barb portion 115. Barb portion115 may be spaced a predefined distance from the proximal end oftransducer 114, thereby defining gap 113. As shown in FIG. 6B, gap 113and barb portion may extend circumferentially around the distal regionof catheter shaft 112. During assembly, outer catheter 116 (not shown)may then be fed over the proximal end of transducer shaft 112 until thedistal end of outer catheter 116 passes over barb portion 115 and gap113 and engages with the proximal end of transducer 114. A material,e.g., epoxy, may be added to fill in the cavity formed between gap 113and the inner surface of outer catheter 116, such that outer catheter116 and transducer shaft 112 are sealed to create a fluidically sealedcavity therebetween.

The outer diameter of outer catheter 116 may be substantially equal tothe outer diameter of transducer 114, and the inner diameter of thelumen of outer catheter 116 may be larger than the outer diameter oftransducer shaft 112, thereby providing a cavity between the innersurface of outer catheter 116 and the outer surface of transducer shaft112. As described above, this cavity may be fluidically sealed. As shownin FIG. 6C, one or more cables, e.g., cable 600, may be positionedwithin the fluidically sealed cavity to provide power to transducer 114.For example, as shown in FIG. 6C, cable 600, which may be electricallyinsulated along almost its entire length, may include conductive portion602 for electrically coupling with transducer 114.

To limit the heating of the coaxial cable during pulse generation, alarger conductor profile of cable 600 may be selected; however, having acable with a greater profile would require a larger profile/thickercatheter. Accordingly, instead of a single cable, multiple smallercoaxial cables may be disposed along the length of elongated shaft 101,e.g., within the fluidically sealed cavity, to double thecross-sectional area of the conductor without adding significantthickness to elongated shaft 101.

In addition, a pair of thermocouples, e.g., thermocouple 604 also may bepositioned within the fluidically sealed cavity. FIG. 6D is across-sectional view of the transducer assembly where cable 600 andthermocouple 604 enters the proximal end of barb portion 115 oftransducer shaft 112. For example, thermocouple 604 may be a type Tthermocouple for monitoring the transducer temperature at the interfacewith the blood flow. Thermocouple 604 may be located on the innersurface of the copper tape. As the copper and the silver electrode arevery good thermal conductors, the temperature measured at this locationis representative of the temperature of the transducer's outer surface,without interfering with the acoustic beam, nor adding additionalthickness to the transducer assembly build.

Moreover, one or more radiopaque markers may be located on thetransducer assembly to allow the user to determine the positioningand/or orientation of transducer 114 within the patient. For example,one or more radiopaque markers may be disposed in two perpendicularplanes to each the positioning. Accordingly, when the transducer isconfigured such that at least a portion of the transducer emits less orno energy, e.g., forming a dead zone, as described in further detailbelow, the radiopaque markers may assist the user in determining whichdirection the dead zone is directed, so as to avoid sensitive anatomicalstructures, e.g., the phrenic nerve, the recurrent-Laryngeal nerve, orthe airways, during the ablation procedure, e.g., creating a lesion onthe other areas around the pulmonary artery.

Referring now to FIG. 7 , method 700 for treating tissue using thecatheter systems described herein is provided. At step 702, anintroducer may be set up. For example, the introducer may be insertedthrough an entry site in the patient, e.g., a venous access point, andfixed relative to the patient. At step 704, the distal end of aguidewire may be inserted through the introducer and advanced into thetarget vessel, e.g., the pulmonary artery. For example, a Swan-Ganzcatheter may first be inserted into the access point and floated to thetarget location within the target vessel. The guidewire may then beadvanced through the Swan-Ganz catheter, and the Swan-Ganz catheter maybe removed, leaving the guidewire in place from the access point to thetarget location. The guidewire may be steered, for example, underfluoroscopy from the access point to the target location.

At step 706, the proximal end of the guidewire, which is external to thepatient, may be inserted into the catheter system, e.g., through thelumen of inner catheter 110 via tip 111. At step 708, handle 300 may beactuated to collapse anchor 200, e.g., an expandable frame, and toresheath anchor 200 within sheath 118. For example, as described above,knob 304 may be actuated to move inner catheter 110 distally relative toouter catheter 116 to cause anchor 200 to transition to the collapseddelivery state, then knob 306 may be actuated to move sheath 118distally relative to anchor 200 until anchor 200 is disposed withindistal region 118 b of sheath 118, and the distal end of distal region118 b engages with tip 111. At step 710, distal region 104 of cathetersystem 100 may be advanced over the guidewire and through the introduceruntil transducer 111 is positioned within the target location within thetarget vessel. In some embodiments, catheter system 100 may includefeatures of a Swan-Ganz catheter such as a floatable balloon, such thatdistal region 104 of catheter system 100 may be inserted into the accesspoint and floated to the target location.

At step 712, handle 300 may be actuated to unsheathe anchor 200, and todeploy anchor 200 within the target vessel. For example, as describedabove, knob 306 may be actuated to move sheath 118 proximally relativeto anchor 200 until anchor 200 is exposed from sheath 118, then knob 304may be actuated to move inner catheter 110 proximally relative to outercatheter 116 to cause anchor 200 to transition to the expanded deployedstate within the target vessel. At step 714, transducer 114 may beactuated to emit energy, e.g., ultrasonic energy, to the target vesselto reduce neural activity of nerves surrounding/innervating the targetvessel. For example, transducer 114 may be actuated to emit energy inaccordance with a predetermined ablation regime. The predeterminedablation regime may be selected to, e.g., to prevent overexposure and/orover ablation of the blood vessel. For example, the predeterminedablation regime may include predetermined periods of non-ablation wheretransducer 114 does not emit energy, or alternatively emits a reducesamount of energy, between predetermined periods of ablation wheretransducer 114 emits energy within the blood vessel. For example, thepredetermined ablation regime may cause transducer 114 to emit energyfor, e.g., ten seconds, then emit no energy for, e.g., five secondsbefore emitting energy for another ten seconds, and so on.

Transducer 114 may be operatively coupled to a generator for supplypower to transducer 114, e.g., via conductive portion 602 and cable 600.The generator may be programmed with one or more control loops to ensuresafe ablation by transducer 114. During sonication/ablation, thetransducer dissipates in Joule effect the energy which was not convertedinto acoustic energy, thereby increasing the transducer temperature.Heating of the transducer surface may vary upon transducer builds,depending on their respective efficiency. Energy in a low efficientbuild will dissipate in Joule effect causing blood flow to be exposed toa higher temperature across the transducer. Blood flow across thetransducer acts as a natural coolant for the transducer, e.g., as anchor200 is non-occlusive, however, if blood is heated due to the transducertemperature above a given temperature threshold, fibrinogen in the bloodmay be denatured, leading to dangerous clots. The transducer temperatureis a function of/proportional to the power applied to it, and thus, acontrol loop may be implemented by the generator to adapt the powerdelivery to a temperature target if a temperature threshold is exceeded.The control loop further may take into account temperature variationsdue to other factors such as the pulsatile flow of blood.

As shown FIG. 13 , the temperature monitoring allows the generator tostop the energy delivery if the temperature threshold is exceeded for apredetermined period of time, e.g., the max duration over threshold. Forexample, if transducer temperature, e.g., as measured via thermocouple604 coupled to the generator, is below the temperature threshold, thegenerator may provide an amount of electrical power corresponding to theamount requested by the user/catheter system 100. Once the temperaturethreshold is exceeded, the control loop adapts the electrical power toprevent the transducer temperature from exceeding a target temperature.If the transducer temperature exceeds the safety threshold for morethan, e.g., 2 seconds, the generator may cease power delivery totransducer 114. As an example, the temperature threshold may be definedbetween 50° C. and 56° C. and the acceptable time above the thresholdmay be defined between 0 and 4 seconds.

In addition, anatomical airway structures adjacent to transducer 114 mayreflect acoustic energy back to transducer 114 during an ablationprocedure. Transducer 114 may convert the reflected acoustic energy intoelectrical energy, which may be measured by the generator. Thus, theelectrical energy measured by the generator would be higher than if anairway was not present. Accordingly, the generator may detect thepresence of the airway structure based on the increased electricalenergy converted by transducer 114, which is indicative of a level ofacoustic energy reflected from an adjacent airway structure, and thecontrol loop may be tuned to shut off sonication upon detection of anearby airway structure.

As opposed to the nerves located in the adventitia of the pulmonaryartery vessel, the transducer is exposed to the blood flow which is anexcellent coolant. As a consequence, temperature slope when the pulse isstopped is greater in the transducer than in the tissue. To control thetransducer temperature with a limited effect on the temperature build upat the lesion location, use of a duty cycle in the transducer electricalsource is able to maximize the output power without proportionallyincreasing the off-time of the overall pulse duration.

Moreover, to increase the thermal energy dissipation of the transducer,a heatsink may be added at the proximal or the distal end of thetransducer. For example, the heatsink may be a transducer end cap or aproximal support frame formed of stainless steel having a contact areawith the blood that is between, e.g., 1 cm² and 3 cm². Alternatively,the proximal support frame may be connected to the anchor frame formedof nitinol or stainless steel to spread the transducer thermal energy tothe entire surface of the anchor, which may represent between 5 cm² and30 cm² of surface area in contact with the blood flow.

At step 718, upon completion of the ablation therapy, handle 300 may beactuated to resheath anchor 200 as described above, and catheter system100 may be removed from the patient. At step 720, the guidewire and theintroducer may be withdrawn from the patient, and the entry site, e.g.,venous puncture, may be closed.

FIG. 8 schematically illustrates the general anatomy of the heartincluding pulmonary arteries and catheter system 100. The access pathwayillustrated in FIG. 8 is one example of many possible access pathwaysfor use with catheter system 100. As shown in FIG. 8 , anchor 200 may bedeployed within the left pulmonary artery LPA to secure and centralizetransducer 114 within the LPA. Anchor 200 and transducer 114 areoperatively coupled to handle 300, external to the patient, viaelongated shaft 101 of catheter system 100.

Elongated shaft 101 is generally advanced through the vasculature andheart to a target location in the vasculature. As shown in FIG. 8 ,elongated shaft 101 may be advanced through an access point in aperipheral vessel, such as the right femoral vein RFV, into the inferiorvena cava IVC, through the right atrium RA of the heart H, into theright ventricle RV, and then through the pulmonary trunk PT to the leftpulmonary artery LPA. Other anatomical structures labeled in FIG. 8include the right pulmonary artery RPA, branching vessels BV, superiorvena cava SVC, and left femoral artery LFA. Alternatively, elongatedshaft 101 may be advanced through an access point in the LFV, into theinferior vena cava IVC, through the right atrium RA of the heart H, intothe right ventricle RV, and then through the pulmonary trunk PT to theleft pulmonary artery LPA. Accordingly, elongated shaft 101 may have alength between about 100 cm and about 150 cm (e.g., about 100 cm, about110 cm, about 120 cm, about 130 cm, about 140 cm, about 150 cm, andranges between such values).

Alternatively, elongated shaft 101 may be advanced through an accesspoint in a jugular vein, ulnar vein, etc., into the SVC, through theright atrium RA of the heart H, into the right ventricle RV, and thenthrough the pulmonary trunk PT to the left pulmonary artery LPA.Accordingly, elongated shaft 101 may have a length between about 60 cmand about 120 cm (e.g., about 60 cm, about 75 cm, about 90 cm, about 105cm, about 120 cm, and ranges between such values).

The target location may be any of a number of locations, for example,the pulmonary trunk PT, the left pulmonary artery LPA, the rightpulmonary artery RPA, any of the branching vessels BV, the ostia of theleft pulmonary artery LPA and/or right pulmonary artery RPA, and/or thelike. Moreover, a different access method may be used, and a pulmonaryvein or other pulmonary venous vasculature may be the target location.Additional access routes and potential targets are described in furtherdetail herein.

Once at the target site, transducer 114 may be actuated to interrupt thenerves around the left, right, and/or main pulmonary arteries, e.g.,neuromodulation. Neuromodulation may be accomplished (e.g., viaablation, denervation, which may or may not be reversible, stimulation,etc.), for example using acoustic energy (e.g., ultrasound), microwaveenergy, radiofrequency (RF) energy, thermal energy, electrical energy,infrared energy, laser energy, phototherapy, plasma energy, ionizingenergy, mechanical energy, cryoablation, chemical energy, pulsed fieldelectroporation, combinations thereof, and the like.

Pressure measurements within a blood vessel during distension of theblood vessel may be analyzed to confirm successful reduction of neuralactivity of nerves surrounding the target blood vessel, e.g., via thecatheter systems described herein. Specifically, when a blood vesselhaving active nerves is distended, e.g., by applying a sufficient forceto the inner wall of the blood vessel, baroreceptors within the bloodvessel may be stimulated, thereby causing a corresponding increase inpressure within the blood vessel. However, data indicates that when theneural activity of the nerves surrounding the blood vessel has beenreduced/inactivated, distension of the blood vessel either does notresult in a corresponding increase in pressure within the blood vesselor results in a much smaller increase in pressure within the bloodvessel. Accordingly, by comparing the pressure gradients within theblood vessel during distension of the blood vessel before and after anablation procedure, successful reduction of neural activity of thenerves surrounding the blood vessel may be confirmed.

Referring now to FIG. 9 , method 900 for confirming reduction of neuralactivity of nerves is provided. At step 902, first pressure informationmay be measured within the target blood vessel, e.g., the pulmonaryartery, at a first time. For example, pressure may be measure via one ormore sensors or small transducers, e.g., FFR wires, integrated withcatheter system 100, e.g., proximal and/or distal to transducer 114, orseparate from catheter system 100. Additionally or alternatively,pressure may be measured via commercially available pressure transducerscoupled to a lumen of elongated shaft 101, or pressure transducersinserted into a lumen of elongated shaft 101. The pressuresensors/transducers may be operatively coupled to a controller ofcatheter system 100 for recording and analyzing the pressuremeasurements. The first pressure information may be indicative of apre-ablation baseline pressure within the blood vessel.

At step 904, a first force may be applied to the inner wall of thetarget blood vessel to distend the blood vessel, to thereby stimulatebaroreceptors within the blood vessel wall at a second time. Forexample, the first force may be applied via a distension mechanism. Thedistension mechanism may be an expandable member, e.g., an expandablecage, that may be actuated to transition between a collapsedconfiguration and an expanded configuration wherein the expandablemember applies a force to the inner wall of the blood vessel sufficientto distend the blood vessel. Preferably, the expandable member does notocclude the blood vessel in the expanded configuration. Alternatively,the expandable member may be a balloon configured to be inflated todistend the blood vessel. The expandable member may be disposed on acatheter separate from elongated shaft 101 of catheter system 100, oralternatively, the expandable member may be disposed on distal region104 of catheter system 100, e.g., proximal and/or distal to transducer114. In some embodiments, anchor 200 may be used as the distensionmechanism, such that anchor 200 is expanded, e.g., via inner catheter110 and outer catheter 116, to a diameter greater than the diameter ofthe inner wall of the blood vessel to thereby distend the blood vessel.

Alternatively, the distension mechanism may be a catheter shaft that maybe actuated to form a bend to thereby apply a force to the inner wall ofthe blood vessel sufficient to distend the blood vessel. For example,the catheter shaft may be actuated by a pull-wire that, when pulledproximally via actuation at handle 300, causes the catheter shaft tobend and apply force to the inner wall of the blood vessel at the bend.The bendable catheter shaft may be separate from elongated shaft 101 ofcatheter system 100, or alternatively, the bendable catheter shaft maybe integrated with elongated shaft 101, e.g., elongated shaft 101 may beconfigured to be actuated to form a bend to thereby apply a force to theinner wall of the blood vessel.

At step 906, second pressure information may be measured within thetarget blood vessel while the first force is being applied to the innerwall of the blood vessel. The second pressure information may beindicative of a first pressure gradient between pressure within theblood vessel while the first force is applied to the inner wall todistend the blood vessel and pre-distension pressure within the bloodvessel associated with the first pressure information. The distensionmechanism may then be actuated to cease application of force to theinner wall of the blood vessel.

At step 908, an ablation device, e.g., transducer 114, may be actuatedto emit energy, e.g., ultrasonic energy, at a third time within theblood vessel to ablate nerves surrounding the blood vessel, for example,as described above with regard to method 700. For example, anchor 200may be deployed prior to ablation to centralize transducer 114 withinthe blood vessel. During the emission of energy, when the ablationprocedure is complete, or when the ablation procedure is otherwisepresumed to be complete, at step 910, a second force may be applied tothe inner wall of the target blood vessel, e.g., via a distensionmechanism, to distend the blood vessel at a fourth time, to therebystimulate baroreceptors within the blood vessel wall. In someembodiments, the distension force is continuously applied and pressureis continuously measured during emission of energy such that pressuregradients are monitored in real time to determine when the ablationprocedure has sufficiently reduced neural activity, thereby causingenergy emission to be ceased. Preferably, the same distension mechanismmay be used to apply the first and second force to the inner wall of thevessel. Moreover, the same amount of force is preferably applied duringthe first and second vessel distensions.

At step 912, third pressure information may be measured within thetarget blood vessel while the second force is being applied to the innerwall of the blood vessel. The third pressure information may beindicative of a second pressure gradient between pressure within theblood vessel while the second force is applied to the inner wall todistend the blood vessel and pre-distension pressure within the bloodvessel associated with the first pressure information. The distensionmechanism may then be actuated to cease application of force to theinner wall of the blood vessel.

At step 914, the controller of catheter system 100 may compare thesecond pressure information to the third pressure information todetermine whether the emitted energy has reduced neural activity of thenerves around the blood vessel. Additionally or alternatively, both thesecond and third pressure information may be displayed on a display fora user to manually compare the second and third pressure information todetermine whether neural activity of the nerves around the blood vesselwas successful reduced. Accordingly, a successful ablation therapy maybe measured by a substantial reduction of neural activity or completeinactivation of the nerves as indicated by the comparison of the secondand third pressure information. For example, it may be determined thatthe emitted energy has successfully reduced neural activity of thenerves around the blood vessel if the comparison of the second and thirdpressure information indicates that the second pressure gradient is lessthan the first pressure gradient by more than a predetermined threshold.Moreover, it may be determined that the emitted energy has successfullyreduced neural activity of the nerves around the blood vessel if thesecond pressure gradient is zero, e.g., the post-ablation distensiondoes not result in any increase in pressure within the blood vessel.

If the comparison of the second and third pressure information indicatesthat neural activity of the nerves has not been sufficiently reduced,e.g., the second pressure gradient is not less than the first pressuregradient by more than the predetermined threshold, the steps above maybe repeated, e.g., steps 908-914. For example, transducer 114 may beredeployed if not already deployed, to emit additional energy within thetarget vessel. The target blood vessel may then be distended by applyinga third force to the inner wall of the target vessel, and fourthpressure information may be measured within the target blood vesselwhile the third force is being applied to the inner wall of the bloodvessel, such that the fourth pressure information may be indicative of athird pressure gradient between pressure within the blood vessel whilethe third force is applied to the inner wall to distend the blood vesseland pre-distension pressure within the blood vessel associated with thefirst pressure information. The fourth pressure information may then becompared to the third pressure information and/or the second pressureinformation to confirm with the neural activity of the nerves around thetarget blood vessel has been sufficiently reduced. The method stepsabove may be repeated until confirmation is received that the neuralactivity of the nerves around the target blood vessel has beensufficiently reduced.

To minimize the thickness of the outer diameter of the transducer, e.g.,transducer 114, a conductive ring (e.g., copper) or tape may be used toextend the outer electrode connection and soldering from the innerdiameter of the transducer assembly. To optimize the radiation of thepiezoelectric element of transducer 114 and to reduce the mass loadingeffect due to the outer connection, the copper ring or tape may coverthe full circumference of the outer electrode of transducer 114.Moreover, to control the directivity or the uniformity of the emittedenergy, e.g., the acoustic beam, the inner diameter connection of thetransducer assembly may be made of one or several connections spreadover the inner electrode. Each solder spot over the inner electrodecreates a mass loading and may change the radiation pattern of thetransducer. For example, a wide or thick solder spot may narrow thedirectivity down to 50% at −6 dB from the maximum intensity, while thinsolder spot(s) may lead to a 100% directivity at −6 dB from the maximumintensity, as shown in FIG. 10 .

Additionally, transducer 114 may be covered with a very thin sleeve,e.g., to cover the piezoelectric surface which is not supposed to be abiocompatible material, to provide an electrical insulation for patientprotection, and depending on the drive voltage amplitude and on thematerial dielectric strength, to define thickness of the transducercover. The sleeve further may be thin enough to allow heat dissipationof the transducer in the blood flow during the sonication.

Referring now to FIG. 11 , an alternative distal region of the cathetersystem is provided. Distal region 104′ may be constructed similar todistal region 104, with similar components having like-prime referencenumerals. However, distal region 104′ differs from distal region 104 inthat distal region 104′ may include a plurality of guidewire ports,e.g., guidewire port 1102 disposed on a distal region of outer catheter116′ and guidewire port 1104 disposed on a distal region of distalregion 118 b′ of the sheath. In addition, inner catheter 110′ mayinclude a guidewire port (not shown), such that the proximal end of theguidewire may enter the lumen of inner catheter 110′ via tip 111′, andbe fed through the guidewire port disposed on inner catheter 110′,through guidewire port 1102, and through guidewire port 1104 such thatthe guidewire may extend along an exterior of the elongated shaft of thecatheter system as distal region 104′ is advanced over the guidewire tothe target location within the blood vessel. Accordingly, inner catheter110′ does not need to have a guidewire lumen extending through itsentire length, which would permit inner catheter 110′ to have a smallerprofile proximal to its guidewire port. Accordingly, the profile of allthe components of the elongated shaft proximal to distal region 104′ maybe significantly reduced to reduce the stiffness of the elongated shaft,and therefore ease navigation and prevent heart straining during theprocedure.

As described above, anchor 200 may be lasercut, e.g. from a metallichypotube. In some embodiments, the anchor may undergo an extensiveelectropolishing treatment to render all of the edges of its pluralityof struts round, thereby making the anchor safe to contact the patientanatomy during catheter delivery and/or during displacement fromablation site to ablation site. Accordingly, in this configuration, thecatheter system would not require a sheath to be disposed over theanchor during delivery and displacement from ablation site to ablationsite. Moreover, as the sheath would not be required, the separationsleeve also may not be required as the neither the transducer nor theanchor would need to be stabilized while a sheath is moved relative tothe transducer and anchor. Thus, the profile of the elongated shaft ofthe catheter system would be significantly reduced, e.g., by thethickness of the sheath and the separation sleeve. In addition, theprofile of the tip at the distal end of the inner catheter also may bereduced. As there may not be a need for a sheath or a separation sleeve,the corresponding hubs in the handle may be removed, thereby alsoreducing the profile of the handle.

Moreover, as the profile of the distal region of the catheter systemdictates the size of the puncture required in the patient, e.g., at avenous access point, a distal region having a smaller profile would bemore favorable to healing as well as reduce risk of infection, e.g.,when the puncture is made in the groin area. To reduce the profile ofthe distal region, which is formed by the transducer, the anchor, andthe sheath, the frame may be disposed distal to the transducer in boththe collapsed delivery state and the expanded deployed state. Forexample, a proximal end of the anchor may be coupled to a distal end ofthe transducer shaft extending through the transducer and the tip of theinner catheter.

Referring now to FIG. 12 , and alternative exemplary handle is provided.Handle 300′ may be constructed similar to handle 300, with similarcomponents having like-prime reference numerals. Handle 300′ differsfrom handle 300 in that handle 300′ includes pusher 1200. Pusher 1200 isoperatively coupled to the transducer at the distal region of thecatheter system and is configured to be actuated to move the transducertransitionally relative to the frame. Accordingly, in thisconfiguration, the transducer may be longitudinally moved relative tothe outer catheter and the inner catheter. Thus, the transducer may becoupled to a transducer catheter that is slidably disposed within theouter catheter, such that the proximal end of the anchor remains coupledto the outer catheter. Moreover, the transducer catheter may have alumen sized and shaped to slidably receive the transducer shaft therein,and may be sealed to the transducer shaft to form a fluidically sealedcavity between the transducer shaft and transducer catheter, instead ofthe outer catheter being sealed to the transducer shaft.

Thus, pusher 1200 may be operatively coupled to the transducer assembly,e.g., the transducer shaft, the transducer, and the transducer catheter,such that actuation of pusher 1200 causes translation movement of thetransducer shaft, the transducer, and the transducer catheter relativeto the anchor. Accordingly, the transducer assembly could move relativeto the anchor to perform a plurality of ablations without collapsing andredeploying the anchor, as described in further detail below with regardto FIGS. 22A and 22B. As further shown in FIG. 12 , both inner catheterhub 308′, which is operatively coupled to the inner catheter, and outercatheter hub 310′, which is operatively coupled to the outer catheter,may be operatively coupled to knob 304′, such that actuation of knob304′ causes relative movement of the inner catheter and the outercatheter in equal and opposite directions.

Notably, the denervation around the pulmonary artery may interceptseveral adjacent anatomical structures, such as the aorta, the venacava, the pulmonary veins, the phrenic nerve, the recurrent laryngealnerve, the trachea, the bronchus, and the lungs. The aorta, vena cava,and pulmonary veins are protected by the blood that flows into thesevessels, therefore, the heat generated by the absorption of the acousticbeam by the vessel wall is dissipated by the blood flow inside thesevessels. However, this is not the case for non-target nerves, e.g., thephrenic and recurrent laryngeal nerves, which are not nearby avascularized vessel, nor for the airways, e.g., trachea and bronchus,which are filled with air causing the reflection of most of the incidentacoustic beam, thereby causing the target vessel to be up to twiceexposed to the incident energy.

To spare the non-targeted nerves from being damaged by the acoustic beamduring sonication, the transducer may be designed as non-uniform, asdescribed in further detail below with regard to FIGS. 19B to 19D. Forexample, the transducer may be configured such that 50% to 75% of thecircumference of the transducer radiates a sufficient intensity togenerate a lesion between, e.g., 15-33 W/cm², while the remaining 50% to25% radiates half of this intensity. As shown in FIG. 14 , the anglesbetween −180° and +45° are radiating enough to create a lesion (zone1402) with a direct targeting, while the angles between +45° and +180°are not sufficiently exposed to create a lesion unless they arereflected on the airways (zone 1404). The portion of the energy emittedat reduced intensity may be referred to herein as a “dead zone”. Thedead zone may be angled/directed toward the anatomical structure soughtto be avoided during the ablation procedure.

This method requires the orientation of the transducer to be carefullytaken into account during the procedure. Under fluoroscopy, a radiopaquemarker band may be disposed on transducer 114 to enable the user todetermine to location of the dead zone. The radiopaque marker may havean axially asymmetrical shape, such as a ‘L’ or a ‘P’, so the operatormay readily discern the orientation of the transducer. For example, oneor more radiopaque markers may be disposed in two perpendicular planesto each the positioning.

Referring now to FIG. 15 , an alternative exemplary catheter system isprovided. Elongated shaft 101″ may be constructed similar to elongatedshaft 101, with similar components having like-double prime referencenumerals. However, elongated shaft 101″ differs from elongated shaft 101in that elongated shaft 101″ may include torque shaft 1500. Torque shaft1500 may be formed of, e.g., a multi-filar wire. A proximal region oftorque shaft 1500 may be operatively coupled to the handle of thecatheter system, and a distal region of torque shaft 1500 may be coupledto transducer 114″, such that torque shaft 1500 may be actuated via thehandle to rotate transducer 114″. Accordingly, torque shaft 1500 mayhave a lumen sized and shaped to slidably receive inner catheter 110″therein, and may be disposed within outer catheter 116″. As innercatheter 110″ is fixed to tip 111″, inner catheter 110″ may remainstationary as torque shaft 1500 causes rotation of transducer 114″.Preferably, rotation of transducer 114″ is limited to 180° in bothdirections from a neutral configuration so as to avoid wrapping of thecables/electrical wires around torque shaft 1500.

Referring now to FIG. 16 , another alternative exemplary catheter systemis provided. Distal region 104′″ of the catheter system may beconstructed similar to distal region 104, with similar components havinglike-triple prime reference numerals. However, distal region 104′″differs from distal region 104 in that distal region 104′″ may includeone or more intravascular imaging transducers, e.g., intravascularultrasound (IVUS) transducers. IVUS transducer 1600 is configured toprovide intravascular imaging to permit a user to detect adjacentairways or other sensitive anatomical structures within a field of viewof IVUS transducer 1600, e.g., trachea and bronchial airways, laryngealand phrenic nerves, pericardium, aorta, etc. IVUS transducer 1600 may bea solid-state ultrasound imaging transducer or a rotation piezoelectricultrasound imaging transducer.

IVUS transducer 1600 may generate data used to measure the distancebetween the pulmonary artery and an adjacent airway. The data mayillustrate the airway as a lumen, but may further illustrate a reflected“blind spot” from the cartilage. Accordingly, transducer 114′″ may berotated, as described above with regard to FIG. 15 , to align the deadzone of energy emission, as described above with regarding to FIG. 14 ,with the blind spot to avoid ablating the airway, or otherwise directenergy emission away from the airway. As shown in FIG. 16 , a first IVUStransducer may be positioned on inner catheter 110′″ between the distalend of anchor 200′″ and tip 111′″, a second IVUS transducer may bepositioned on outer catheter 116′″ between transducer 114′″ and theproximal end of anchor 200′″, and/or a third IVUS transducer may bepositioned on outer catheter 116′″ proximal to the proximal end ofanchor 200′″. As will be understood by a person having ordinary skill inthe art, more or less IVUS transducers may be integrated in distalregion 104′″ of the catheter system, and may be positioned on differentlocations along distal region 104′″ than what is illustrated in FIG. 16.

As adjacent sensitive anatomical structures may be imaged via IVUStransducers 1600 such that the dead zone of the transducer may beoriented to avoid the anatomical structure, it important for the user toknow the direction that the dead zone of the transducer is currentlypointing. As shown in FIG. 17A, shield 1702, e.g., a strip of metal or aportion of a cut metal hypotube, may be disposed on IVUS transducer1600, to thereby mask a portion of the image generated via IVUStransducer 1600. Accordingly, shield 1702 may be oriented, e.g., asdescribed above with regard to FIG. 15 , to align shield 1702 with thedead zone of transducer 114′″.

As shown in FIG. 17B, IVUS transducer 1600 may provide imaging of airway1706 within field of view 1708. Rotating IVUS transducer 1600 andtransducer 114′″ would rotate the blind spot on the image as well as thedead zone of transducer 114′″. Accordingly the blind spot and the deadzone may be aligned with airway 1706 to avoid ablation of airway 1706.In this configuration, both IVUS transducer 1600 and transducer 114′″are disposed on the torque shaft, as described above with regard to FIG.15 .

Referring now to FIG. 18 , another alternative exemplary catheter systemis provided. Distal region 104″″ of the catheter system may beconstructed similar to distal region 104, with similar components havinglike-triple prime reference numerals. However, distal region 104″″differs from distal region 104 in that distal region 104″″ includes oneor more pacing electrodes 1800 disposed thereon. As shown in FIG. 18 ,pacing electrodes 1800 may be disposed on anchor 200″″, such that pacingelectrodes 1800 may contact the inner wall of the blood vessel.Additionally or alternatively, pacing electrodes 1800 may be disposed onone or more expandable members proximal and/or distal to anchor 200″″.The phrenic nerve runs along the main pulmonary artery, and controlsdiaphragm movements, e.g., hiccups. Pacing electrodes 1800 may pace theblood vessel to detect the location of the phrenic nerve and/or preventdamage to the phrenic nerve by cutting off ablative energy by a controlloop of the generator upon detection of the phrenic nerve. For example,pacing electrodes 1800 may pace the blood vessel prior to ablation todetermine whether a phrenic nerve is present in the target ablationlocation within the blood vessel. This may be indicated by aphysiological response from the patient, e.g., a hiccup-like reflex, ifa phrenic nerve is located around the blood vessel being paced thatcorresponds with the pacing pulse of pacing electrodes 1800. Thephysiological response may be measured by a clinician, e.g., by feelingthe patient's diaphragm during pacing. Accordingly, this portion of theblood vessel may be avoided (not ablated) to avoid damaging the phrenicnerve. Moreover, pacing electrodes 1800 may pace the blood vessel duringablation by transducer 114″″ to detect any abnormalities during thepacing indicative of damage to the phrenic nerve. For example, if aphrenic nerve is detected via pacing by pacing electrodes 1800, theclinician may feel the physiological response by the patient during theablation procedure, such that a change in the frequency and/or intensityof the physiological response may be indicative of damage to the phrenicnerve. Accordingly, the user may stop ablation if such a change inphysiological response due to pacing is detected during the ablation. Aswill be understood by a person have ordinary skill in the art, more orless than four pacing electrodes may be integrated with distal region104″″, as shown in FIG. 18 .

FIG. 19A illustrates an example transducer 1900. Transducer 1900 may bepositioned at or near a distal portion of a catheter system (e.g.,catheter system 100). Transducer 1900 may be separate from any anchor(e.g., as described herein). Transducer 1900 may be coupled to a shaft(e.g., elongated shaft 101). Transducer 1900 may comprise hole 1902extending therethrough, for example for coupling to a wire or tube of acatheter. Guidewires or sensor wires may extend through hole 1902. Insome embodiments, transducer 1900 is an arcuate ultrasound transducercomprising a piezoelectric element.

The outer diameter of the transducers described here including, e.g.,transducer 1900, may be between about 3 mm and about 10 mm (e.g., about3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about9 mm, about 10 mm, and ranges between such values). The transducer mayhave a length between about 5 mm and about 30 mm (e.g., about 5 mm,about 10 mm, about 15 mm, about 20 mm, about 25 mm, about 30 mm, andranges between such values). A longer and/or thicker transducer cangenerally provide more power. A shorter and/or thinner transducer may beeasier to navigate through vasculature. A thinner transducer may be usedwith a smaller incision, which can reduce scar size, infection sitesize, and/or healing time. A ratio between the diameter of thetransducer and the length of the transducer may be between about 1/20and about 2/1 (e.g., about 1/20, about 1/15, about 1/10, about 1/5,about 1/3, about 1/1, about 3/2, about 2/1, and ranges between suchvalues).

FIG. 19B illustrates another example transducer 1910. Transducer 1910may comprise a first hemicylinder 1912 a and a second hemicylinder 1912b. First hemicylinder 1912 a and second hemicylinder 1912 b may becoupled to form a cylindrical shape. First hemicylinder 1912 a may beactivated for ablation while second hemicylinder 1912 b is inactive.Partial activation can provide partial circumferential ablation, forexample, to protect sensitive structures in the area around secondhemicylinder 1912 b. First hemicylinder 1912 a may be activated forablation and second hemicylinder 1912 b may be activated for ablation.Coordinated activation can provide full circumferential ablation, forexample, to treat tissue all around a vessel. Full circumferentialablation, as can be provided by the transducer assemblies providedherein, can reduce or eliminate rotation at an ablation site. In someembodiments, transducer 1910 is an arcuate ultrasound transducercomprising a piezoelectric element.

FIG. 19C illustrates another example transducer 1920. Transducer 1920may comprise a plurality of angular or wedge-shaped arcuate regions1922. Eight angular regions 1922 are depicted in FIG. 19C, but anynumbers of regions may be used (e.g., two regions (e.g., as shown inFIG. 19B), three regions, four regions, five regions, six regions, sevenregions, eight regions (e.g., as shown in FIG. 19C), nine regions, tenregions, eleven regions, twelve regions, and ranges between thesevalues). Regions 1922 can all be the same, e.g., include the samematerial, shape, dimension, and/or the like. Alternatively, at least oneof regions 1922 may be different than at least one other of regions1922. For example, a difference may include a material, a shape, adimension, and/or the like.

In another embodiment, the transducer may be divided asymmetrically intotwo independently actuatable regions, e.g., the circumference of thetransducer may be divided into 10-90%, 15%-85% or 25-75%, etc. Forexample, when divided 10-90%, one region will consume 10% of thecircumference of the transducer while the other region consumers 90% ofthe circumference of the transducer. Accordingly, the 90% region may beactuated to emit energy during the ablation procedure while the 10%region does not emit energy, thereby forming a “dead zone” of thetransducer where energy is not emitted. As described above, thetransducer may be rotated via to a torque shaft, such that the dead zonemay be angled/directed toward sensitive anatomical structures nearby toavoid damaging the anatomical structures.

The angular regions 1922 may be activated through a plurality wires1926, each connected to an ultrasound system and to one or more ofregions 1922. In some embodiments, the user may decide which regions1922 to activate during ablation. For example, the angular regions 1922in FIG. 19C that are shaded are activated for ablation while the angularregions unshaded are not activated for ablation. Regions 1922 facingsensitive structures may not be activated to preserve those sensitivestructures from being ablated. A larger quantity of regions 1922 canprovide more activation flexibility in certain such embodiments. Asmaller quantity of regions 1922 can provide less manufacturingcomplexity. In some embodiments, each angular region 1922 comprises aspring contact pad that can allow electrical power to flow through thedisc when the disc is over region 1922.

FIG. 19D illustrates an example transducer connection implementation inwhich stacked discs 1924 that rotate on the edge of transducer 1920 canelectrically connect or disconnect the angular regions 1922. As shown inFIG. 19D, the angular regions 1922 that are shaded are electricallyconnected via stacked discs 1924 and can be collectively activated forablation. The angular regions 1922 are not connected via stacked discs1924 cannot be activated for ablation. In some embodiments, stackeddiscs 1924 may be rotated independently through push and pull wires. Insome embodiments, stacked discs 1924 comprises a single half disc 1924,two stacked half discs 1924, a single two-thirds disc 1924, a singlethree-quarters disc 1924, etc. Discs 1924 can provide an ablationprofile that inhibits or prevents ablation in a region where a sensitivestructure or other structure desirably not ablated is located. Therotation of the disc 1924 can be controlled from the proximal side ofthe catheter, for example, through a wheel that rotates a shaft withappropriate torquability. Two radiopaque symbols located on theactuating shaft can inform the operator about the positioning of discs1924 and thus about the ablation profile that is or would be created.

Referring again to FIG. 8 , elongated shaft 101 may need to navigatesomewhat tortuous anatomy, including, for example, a right turn into theright atrium followed soon by a U-turn in the right ventricle. If anyportion of elongated shaft 101 is too stiff or not flexible enough tomake such turns, then distal region 104 might not be able to bedelivered to the target location(s). FIG. 19E schematically illustratesan example transducer 1950 comprising a plurality of longitudinalsegments 1952. Transducer 1950 may comprise any suitable quantity oflongitudinal segments 1952 (e.g., two segments, three segments, foursegments (e.g., as shown in FIG. 19E), five segments, six segments, andranges between such quantities). More segments 1952 are also possible.Segments 1952 can be abutting or spaced apart by a distance. Segments1952 may be spaced during navigation and then an actuator (e.g.,controlling a pull wire and/or push rod) can cause the segments to abutduring ablation. Transducer 1950 can ease the bending of the distalportion of the catheter during navigation to the target location(s)because the catheter is able to bend between segments 1952. In someembodiments, segments 1952 can provide electronic focusing of anultrasound beam using phased wave generation. Segments 1952 may bepartially activated, for example, similar to the hemicylinder portions1912 a, 1912 b and/or angular regions 1922 described herein. Forexample, one, some, or all of segments 1952 may be activated forablation depending on where the targeted nerves for ablation are locatedand where sensitive structures may be located.

FIGS. 20A to 20D illustrate example outer surface shapes of exampletransducers. FIG. 20A is an end view or a cross-sectional view of atransducer 2020 having a round outer shape 2022. The outer surface oftransducer 2020 does not need to be a perfect circle. For example,transducer 2020 may be oval, elliptical, egg-shaped, etc. Transducer2020 having an outer surface shape being round or arcuate can provide anultrasound beam that is projected out in all directions, for example asschematically shown in FIG. 20A. An ultrasound beam projecting out inall directions can allow for ablation to occur around all areassurrounding a vessel wall at an ablation site, which optionally reducesor eliminates rotation of the transducer 2020 because an entirecircumferential area can be treated with one ablation. Using only oneablation can reduce procedure time. Reduced procedure time for a targetlocation can be especially important, for example, when multiple targetlocations are treated (e.g., multiple locations in the RPA, LPA, andPT), and/or if an anchor is collapsed and then re-expanded betweenablations.

FIGS. 20B to 20D illustrate additional example outer surface shapes oftransducers. FIG. 20B is an end view or a cross-sectional view oftransducer 2024 having an octagonal outer shape. FIG. 20C is an end viewor a cross-sectional view of transducer 2026 having a decagonal outershape. FIG. 20D is an end view or a cross-sectional view of transducer2028 having a dodecagonal outer shape. Transducers having any number ofpolygonal sides, preferably greater than five and less than 32, are alsopossible. While not a perfect circle, a higher number polygon outershape can function similarly to a round outer shape in that theultrasound beams projected out are in all directions from the transducerand produce a large amount of coverage. The transducer does not have anoverall flat shape. For example, the transducer is not flat, two-sided,triangular, square, trapezoidal, parallelogram, or rectangular.Transducers of flat shapes, such as those listed herein, may not be ableto provide a complete projection of ultrasound energy, and/or mayrequire rotating the transducer to ablate all targeted nerves.

The transducers 2022, 2024, 2026, 2028 may include a plurality ofhemi-pieces or wedge-shaped regions (e.g., as described with respect toFIGS. 19B and/or 19C), a plurality of longitudinal segments (e.g., asdescribed with respect to FIG. 19E). Such regions and/or segments may beindividually, partially, and/or collectively activated, as desired.

Any one of the transducers described herein or other transducers mayoptionally be coupled to a lens to focus or defocus the ultrasoundenergy. For example, energy from a cylindrical transducer can be focusedby a lens to produce a toroid or doughnut-shaped treatment region aroundthe transducer. Other shapes are also possible (e.g., spherical,ellipse, egg, arch, hemisphere, cigar, disk, plate, bulged versionsthereof, etc.). The transducer may be acoustically coupled to the lenswith piezoelectric material. The combination of the transducer and thelens may be called a transducer assembly, which may include the couplingmaterial. In certain embodiments in which the device does not include alens, the reference to a transducer assembly herein may refer to thetransducer itself and optionally related components such as a conductorwire, material to couple the transducer to the shaft, etc. The focallength may be affected by the profile of the lens, the energy applied tothe transducer, the efficiency of the components and/or assembly, and/orother parameters. In some embodiments, the efficiency of the assembly istested by the manufacturer or a testing laboratory and the knownefficiency is used during treatment.

FIG. 21A illustrates an example Fresnel lens 400. Lens 400 isacoustically coupled to a transducer. Fresnel lens 400 comprises aplurality of prisms configured to change the direction of the acousticenergy from the transducer so that the energy is generally focused to acommon longitudinal area. The Fresnel lens can reduce the overalldiameter of a catheter system, e.g., catheter system 100, and/or aportion thereof (e.g., a distal portion) because the prisms are able toredirect energy while maintaining a low profile (e.g., compared to aconvex surface that may have a diameter that increases towards thelongitudinal edges). FIG. 21B schematically illustrates example energyrays emanating from the prisms to longitudinally focus and concentrateacoustic energy to a smaller section 2102 around the transducerassembly. In practice, section 2102 can be tissue surrounding a vesselin which the transducer is positioned. In some embodiments, for a 22 mmfocal point measured from the center of the transducer radially outward,a lesion that can be created by the energy may be pre-focal (e.g., about1.5-5 mm from the vessel wall, depending on vessel diameter and otherparameters). A larger amount of energy delivered and/or a longerdelivery duration can increase the focal depth. A smaller amount ofenergy delivered and/or a shorter delivery duration can reduce the focaldepth. The focus point of the energy does not have to be a pinpointlocation or band. FIG. 21C illustrates an example portion of an energyapplication shape. Part of a toroidal area 2105 is illustrated. Theenergy application shape may be a full toroid, but shown in FIG. 21C asonly part of a toroid for clarity. In some embodiments, the partialtoroid shown in FIG. 21C may be created, for example, by activation ofless than an entire transducer (e.g., one, two, or some wedges). Theenergy produced by a transducer may be at least partially absorbed bytissue in and/or around the vessel, which can create the toroidalablation site 2105. Other energy application shapes are also possible(e.g., spherical, ellipse, egg, arch, hemisphere, cigar, disk, plate,bulged versions thereof, etc.).

The lens preferably comprises one or more materials that areacoustically conductive, good thermal conductors, good electricalinsulators, and/or biocompatible. No one material may possess all ofthese properties, so a plurality of layers can be used (e.g., theouter-most layer can be biocompatible to protect the body from innerlayers that are not as biocompatible). In some embodiments, the lenscomprises aluminum that has been anodized or otherwise treated to have acoating of aluminum oxide (alumina). The aluminum and alumina are bothgood thermal conductors, the aluminum is acoustically conductive (e.g.,the speed of sound through aluminum is about 4× the speed of soundthrough blood), and the alumina is biocompatible and a good electricalinsulator. In some embodiments, the lens comprises silicon dioxide.Silicon dioxide is a good thermal conductor and biocompatible, and withcertain doping, for example, may be suitably acoustically conductive.

FIG. 21D illustrates an example transducer assembly. The assemblyincludes another example of lens 2110 coupled to a transducer (e.g., asdescribed herein). Lens 2110 may be an ultrasonic lens. FIG. 21D is across-sectional view through the longitudinal axis L and depicts atransducer assembly comprising a cylindrical transducer 2130 and anultrasonic lens 2110. Lens 2110 has an inner cylindrical surface and anouter surface shaped with a concave profile. Lens 2110 is acousticallycoupled to the transducer 2130. The transducer assembly also comprisespiezoelectric element 2112. Lens 2110 can focus energy from thetransducer 2130 (e.g., as described herein). Because lens 2110 does notinclude a plurality of prisms, lens 2110 may have a larger diameter thanFresnel lens 400. Lens 2110 may be easier to manufacture than Fresnellens 2100. Lens 2110 may be easier to flush with saline prior toinsertion into vasculature than Fresnel lens 2100.

Lens 2110, or Fresnel lens 2100, increases the surface in contact withblood inside the vessel, which can improve the ability of the transducerto cool down by acting as a heat sink. To act as a heat sink, the lensmaterial is preferably a thermal conductor (e.g., aluminum, alumina,silicon dioxide). The plurality of prisms of Fresnel lens 2100 can actas fins for the heat sink. In some embodiments, lens 2100, 2110comprises biocompatible layer 2114. The lens covers piezoelectricmaterial 2112 of transducer 2130 and inhibits or prevents contactbetween the blood and the outer surface of the transducer. In someembodiments, the lens comprises electrical insulation layer 2116.Insulation layer 2116 isolates the patient from the high voltage used todrive the transducer energy. The lens material may support dielectricproperties to protect the patient from high voltage.

The devices described herein may lack or be devoid of a cooling system,which can advantageously significantly reduce device cost. For example,the blood flow through the pulmonary arteries may be sufficient to coolthe transducer assembly. In contrast, a transducer assembly positionedin a renal artery may not be exposed to sufficient blood flow to provideenough cooling, and such devices may include a cooling system (e.g., asaline lumen pumped through the transducer before, during, and/or afterablation).

The size of a lens may depend, for example, at least partially on thematerial(s) and/or frequency (e.g., the natural frequency and/or theapplied frequency from the ultrasound beam generator). Frequencyadjustments can be made during the calibration or the setup of thetransducer, for example so such adjustments do not need to be madeduring a procedure. Different frequencies may be used to ablatedifferent depths outside the vessel. The material selected for the lensmay impact the frequency needed for ablation. For example, if anacoustically poor material such as glass is used, the lens would bethinner to account for the losses caused by the acoustically poormaterial. If, for example, the material used has good acoustics, thelens may be thinner. For example, for a 25 mm focal length at 3 MHz overa 4 mm outer diameter transducer, an aluminum lens (c=6500 m/s) can havea profile of 5.4 mm, while an epoxy lens (c=2430 m/s) can have a profileof 7 mm for the same focal length.

Each transducer and lens combination has an associated data sheet thatcharacterizes the transducer assembly and accounts for the differencesin the transducer and lens combinations. Since the absorption of theacoustic energy by the tissue is a function of the frequency of theultrasound beam, the transducer assembly should be carefully designed tomeet the desired specifications. In an example implementation, a 4 mmouter diameter transducer is coupled to a 5 mm outer diameter aluminumFresnel lens having a 25 mm focal length for operation at 4.5 MHz. Inanother example implementation, a 4 mm outer diameter transducer iscoupled to a 6 mm outer diameter epoxy Fresnel lens having a 25 mm focallength for operation at 4.5 MHz. In another example implementation, a1.5 mm outer diameter transducer is coupled to a 2.15 mm outer diameteraluminum Fresnel lens having a 10 mm focal length for operation at 6MHz. In another example implementation, a 1.5 mm outer diametertransducer is coupled to a 2.8 mm outer diameter epoxy Fresnel lenshaving a 10 mm focal length for operation at 6 MHz. The catheter maycomprise one or a plurality of flushing ports to inhibit or preventintroducing bubbles inside the patient (e.g., bubbles that mightotherwise be trapped in the prisms of a Fresnel lens).

As described above, during ablation, a transducer assembly (e.g., asdescribed herein) may be anchored within a vessel, e.g., via anchor 200.If the transducer assembly is not anchored, it may float or flop aroundin the blood flow, especially high blood flow like in pulmonaryarteries, which can cause very unpredictable, or at the very leastblurry and inefficient, ablation. Accordingly, the position of thetransducer may be steadied by an anchor.

The anchors described herein may be configured to preserve blood flowthrough the vessel, including when the anchor is in a deployed state. Amethod including the anchor may comprise allowing blood to flow throughthe vessel when the anchor is in a deployed state. In some embodiments,the anchor does not comprise a balloon. For example, the edges of theprisms of a lens (e.g., Fresnel lens 2100) may damage a balloon anchor.In some embodiments, the anchor is not occlusive, allowing blood tocontinue to flow to downstream vessels and organs (e.g., the lungs).Renal denervation devices, for example comprising balloons, aretypically occlusive because it is possible to pause blood flow to thekidneys without negative systemic effects. In some embodiments, a deviceconfigured to be used in pulmonary branch vessels (RPA and/or LPA) maycomprise an anchor that occludes blood flow to one lung at a timebecause the other lung may be sufficient to oxygenate the blood for ashort duration.

FIG. 22A illustrates an example embodiment of anchor 2200 comprising aplurality of struts 2204 in a collapsed or delivery state. Anchor 2200is navigated to a vessel in the delivery or collapsed state. In someembodiments, anchor 2200 may be covered with a sheath during delivery orat other times in the delivery state. Anchor 2200 is deployable towardsa deployed state.

FIG. 22B illustrates anchor 2200 in the deployed state. Depending on thediameter of the vessel, it may not be possible to achieve the deliverystate shown in FIG. 22B, but expansion of anchor 2200 such that anchor2200 is able to maintain a substantially constant position of thetransducer assembly 2201 in the vessel may be considered the deployedstate. Ablation preferably occurs when anchor 2200 is in the deployedstate, or is not in the delivery state.

Plurality of struts 2204 may, for example, be cut (e.g., laser cut) froma hypotube or sheet. Cutting struts 2204 from a tube or sheet may, forexample, provide quick and repeatable manufacturing. In someembodiments, plurality of struts 2204 are discrete wires. The wires areoptionally not cut from a tube or sheet, or may be originally cut from atube or a sheet in a manner that allows at least some of struts 2204 tobe discrete (e.g., not directly coupled by strut material to anotherstrut). Using discrete wires may provide flexibility in determining theshape and configuration of struts 2204. For example, plurality of struts2204 may comprise wires that are straight, twisted, flat, round,combinations thereof, etc. (e.g., as shown in FIGS. 22A-22D). The wiresmay have a polygonal cross-section (e.g., rectangle, square, diamond,trapezoid, bulged versions thereof, etc.), a round or arcuatecross-section (e.g., circle, oval, ellipse, etc.), combinations thereof,and the like.

Struts 2204 may be coupled (e.g., individually coupled) (e.g., adhered,soldered, welded, not separated when being cut from a tube or sheet,combinations thereof, and the like) distal and proximal to transducerassembly 2201. As shown in FIG. 22A, distal portions of struts 2204 arecoupled to a distal shaft 2202 and proximal portions of the struts 2204are coupled to proximal shaft 2212. The distal shaft 2202 may comprisean atraumatic tip. The distal portions of struts 2204 may be coupled tothe distal shaft 2202 distal to transducer assembly 2201. The proximalportions of struts 2204 may be coupled to the proximal shaft 2212proximal to transducer assembly 2201. Transducer assembly 2201 may besubstantially radially centered between struts 2204 in the deliverystate and/or in the deployed state. The distal shaft 2202 islongitudinally movable relative to proximal shaft 2212. Suchlongitudinal movement may be allowed during self-expansion of anchor2200 and/or used to expand anchor 2200. When struts 2204 bow radiallyoutward, the longitudinal distance between the distal portion of thestruts 2204 and the proximal portion of the struts 2204 is reduced.Transducer assembly 2201 may be substantially radially centered betweenthe struts 2204 in the delivery state and/or in the deployed state.

In some embodiments, anchor 2200 is deployed by pushing the proximal anddistal portions of the struts 2204 together (e.g., proximally retractingthe distal shaft 2202 and/or distally advancing the proximal shaft2212), causing the struts 2204 to bow radially outwards, as shown inFIG. 22B. In the deployed state, the plurality of struts 2204 expand outto contact or appose vessel walls. The anchor 2200 may maintain alongitudinal position of the transducer assembly 2201. Thisumbrella-type method of deployment can provide better control of theradial force being applied to the vessel wall by the anchor 2200. If themovement is manual by a hand of a user, for example, the user will beable to feel when the struts 2204 contact the vessel wall and stopexpanding the struts 2204 at the appropriate deployed state. If themovement is motorized, for example, sensors may be used to measure forceand stop movement upon reaching a certain force. To return to a deliverystate, the struts 2204 are pulled apart (e.g., by distally advancing thedistal shaft 2202 and/or proximally retracting the proximal shaft 2212)to collapse the struts 2204 back to the delivery state. The anchor 2200is configured to expand to fit any appropriate size vessel. For example,the LPA, RPA, and PT do not have the same diameters as each other oruniform intra-vessel diameters, and the anchor 2200 is configured toexpand to contact the vessel wall in all suitable locations of the LPA,RPA, and PT. In implementations such as ablation around renal arteries,the anchor 2200 is configured to expand to contact the vessel walls inall suitable locations in the left renal artery and the right renalartery.

The struts 2204 may be self-expanding. For example, the anchor 2200 maybe collapsed and deployed by retracting and advancing an outer sheath2210 to expose or cover the struts 2204. The outer sheath 2210 isproximally retracted in the direction of the arrow 2208 to allow thestruts 2204 to at least partially self-expand. The anchor 2200 isreturned to the collapsed state by distally advancing the outer sheath2210 in the direction of the arrow 2209 to apply a radially inward forceto the struts 2204 to cause the struts 2204 to collapse. In someembodiments, the outer sheath 2210 may be distally advanced to deploythe struts 2204 and proximally retracted to collapse the struts (e.g.,using a push-pull mechanism such as a pull wire extending through thedistal portion 502).

In some embodiments, the outer sheath 2210 may be used withumbrella-type expansion. For example, the outer sheath 2210 may protectthe vasculature from the struts 2204 and vice versa during navigation tothe target location. For another example, the outer sheath 2210 may havea lubricious surface that aids in navigation. For another example, theouter sheath 2210 may hold one or more sensors useful for measuringparameters near the transducer assembly 2201. For another example, theouter sheath may comprise a Swan-Ganz balloon to float the catheter to atarget location (without using a separate Swan-Ganz catheter).

The outer diameter of the distal portion of the catheter including thetransducer assembly 2201, the anchor 2200, and optionally the outersheath 2210 is between about 3 mm and about 12 mm (e.g., about 3 mm,about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 10 mm,about 12 mm, and ranges between such values). A smaller diameter distalportion can allow insertion through a smaller incision. A smallerincision can reduce scar size, potential infection site size, and/orhealing time.

In some embodiments, a combination of partial self-expansion andumbrella-type expansion are used. For example, the outer sheath 2210 maybe proximally retracted, which can allow the struts 2204 to partiallyself-expand. This partial self-expansion may be sufficient to appose thevessel walls. In some alternative implementations in which anchoring isnot desired but spacing between the transducer assembly 2201 and thevessel wall can be provided by the struts being partially self-expanded,this partial self-expansion may be sufficient. If the partialself-expansion is not sufficient (e.g., to sufficiently appose thevessel walls), then the umbrella-type expansion may be used to furtherexpand the struts 2204, for example as described herein.

The plurality of struts 2204 preferably comprise a shape-memory material(e.g., Nitinol, chromium cobalt, MP35N, 35NPT, Elgiloy, etc.). Even inembodiments in which the anchor 2200 is not purely self-expanding,shape-memory material can help the plurality of struts 2204 maintain ashape, respond to external forces (including device-based expansionforces), etc. Other strut materials are also possible (e.g., stainlesssteel).

In some embodiments, the struts 2204 are not aligned with thetransducer. For example, even if the transducer comprises fourwedge-shaped pieces and the anchor 2200 comprises four struts 2204, thestruts 2204 do not necessarily need to be aligned with (e.g., atintersections of) the transducer pieces. Rather, the struts 2204 can beindependent of the transducer pieces.

The transducer assembly 2201 may be substantially radially centeredbetween the struts 2204. If the struts uniformly expand, then thetransducer assembly 2201 may be substantially centered in the vessel.Centering the transducer assembly 2201 in the vessel can help ensurethat tissue all around the vessel is treated. For example, if thetransducer assembly 2201 has a penetration radius of 20 mm and iscentered in a vessel where the diameter of the vessel is 18 mm, then thepenetration depth all around the vessel is about 11 mm. If the sametransducer assembly 2201 was not centered in that same vessel, thenpenetration depth could be 3 mm in one direction and 19 mm in theopposite direction, either or both of which could affect undesiredtissue. It will be appreciated that these numbers are for examplepurposes and that true numbers would take into account, for example,ultrasound absorption, diffraction at interfaces, Snell Descartes' law,etc.

FIGS. 22A and 22B schematically illustrate positions of some exampleradiopaque markers 2270, 2272, 2274, 2276. The marker 2270 is at adistal tip of the distal portion. The marker 2270 may be slightly spacedfrom the distal tip of the distal portion. The marker 2272 is at adistal end of the outer sheath 2210. The marker 2272 may be slightlyspaced from the distal end of the outer sheath 2210. The marker 2274 isat a distal end of the anchor 2200. The marker 2274 may be slightlyspaced from the distal end of the anchor 2200. The marker 2276 is at aproximal end of the anchor 2200. The marker 2276 may be slightly spacedfrom the proximal end of the anchor 2200. In some embodiments, thematerial of the anchor 2200 may be radiopaque such that the marker 2274and/or the marker 2276 is the visible ends of the anchor 2200 (e.g., noseparate marker material is used).

The marker 2270 can be used to control the distal tip of the device, forexample to inhibit or prevent perforation distal to the treatment siteand/or to inhibit or prevent application of pressure on small vessels.The marker 2272 can be used to determine the position of the outersheath 2210, for example relative to other components. If the marker2272 is distal to the marker 2274, the user knows that the anchor 2200is covered by the outer sheath 2210. If the marker 2272 is proximal tothe marker 2276, the user knows that the anchor 2200 is not covered bythe outer sheath 2210. The user may observe the relative positions ofthe markers 2274, 2276 to gauge the expansion of the anchor 2200. Forexample, as seen in FIGS. 22A and 22B, when the markers 2274, 2276 arefurther apart, the anchor 2200 is closer to the collapsed position, andwhen the markers 2274, 2276 are closer together, the anchor 2200 iscloser to the deployed or expanded position. In some embodiments, thedistance between the markers 2274, 2276 can be measured (e.g., directlyusing fluoroscopy measurement (e.g., using the length of the transducer2201 for scale), using indicia on the device, etc.) to determine theextent of expansion, which may include the diameter of the vessel at thedeployment site. The extent of expansion and/or the diameter of thevessel at the deployment site may be used to set neuromodulation (e.g.,ablation) parameters. The radiopaque markers described herein may beimplemented in the other catheter systems described herein, e.g.,catheter system 100.

The transducer assembly 2201 may be longitudinally movable relative tothe distal shaft 2202 and/or the proximal shaft 2212 (e.g., by beingcoupled to an independent transducer shaft). For example, although thetransducer assembly 2201 is illustrated as being large relative to theanchor 2200, the transducer assembly 2201 could extend over a muchsmaller longitudinal extent of the anchor 2200. The transducer assembly2201 could move relative to the anchor 2200 to perform a plurality ofablations without collapsing and redeploying the anchor. For example,the transducer assembly 2201 could be at a first distal position in theanchor 2200, perform a first ablation, then can be proximally retractedto a second intermediate position in the anchor 2200 without moving theanchor 2200, perform a second ablation, then can be further proximallyretracted to a third proximal position in the anchor 2200 without movingthe anchor 2200, and perform a third ablation. In some embodiments, thetransducer assembly 2201 could be at a first proximal position in theanchor 2200, perform a first ablation, then can be distally advanced toa second intermediate position in the anchor 2200 without moving theanchor 2200, perform a second ablation, then can be further distallyadvanced to a third distal position in the anchor 2200 without movingthe anchor 2200, and perform a third ablation. In some embodiments, thetransducer assembly 2201 could be at a first intermediate position inthe anchor 2200, perform a first ablation, then can be distally advancedto a second distal position in the anchor 2200 without moving the anchor2200, perform a second ablation, then can be proximally retracted to athird proximal position in the anchor 2200 without moving the anchor2200, and perform a third ablation. The movability of the transducerassembly 2201 in the anchor 2200 is generally more important than theprecise implementation of movement. While this may be mechanically morecomplex (e.g., as opposed to the transducer assembly 2201 being mountedbetween the distal shaft 2202 and the proximal shaft 2212), suchmovement could reduce operation time by reducing or eliminating thecollapsing, repositioning, and redeploying of the anchor after each ofthe first and second ablations.

The struts 2204 may have a thickness between about 30 μm and about 500μm (e.g., about 30 μm, about 40 μm, about 50 μm, about 60 μm, about 70μm, about 80 μm, about 90 μm, about 100 μm, about 110 μm, about 120 μm,about 130 μm, about 140 μm, about 150 μm, about 500 μm, and any rangesbetween these values). This thickness is measured in the radialdirection of each individual strut 2204. The thinner the struts 2204,the less likely the struts 2204 are to cause interference or scatteringwith an ultrasound signal. For example, the struts 2204 may cast anultrasound shadow resulting in areas covered by the shadow not beingablated.

The plurality of struts 2204 may comprise between about four struts andabout 64 struts (e.g., about four struts, about six struts, about eightstruts, about ten struts, about twelve struts, about sixteen struts,about twenty struts, about thirty struts, about forty struts, aboutfifty struts, about 64 struts, and ranges between such values).

The applicant has discovered that strut thicknesses less than about 100μm does not appreciably affect an ultrasound signal. In embodimentshaving thin struts (e.g., between about 30 μm and about 100 μm), alarger quantity of struts (e.g., between about) may be used to increasethe amount of total apposition force on the vessel wall to providesuitable anchoring.

Some embodiments may comprise thicker struts (e.g., between about 110 μmand about 500 μm). For example, the interference or shadow caused by thethicker struts may be advantageously used to protect a portion of thevessel wall while ablating the targeted tissue (e.g., including nerves)beyond the vessel wall. The thicker struts may provide higher radialforce on the vessel wall for a more secure anchoring.

A balance between reducing interference or a shadow produced by thestruts 2204 and sufficient radial force may be desirable. The number orquantity of struts 2204 may be varied to counteract any interference orshadows and/or to increase radial force as may be appropriate. A lowernumber of struts 2204 can reduce potential interference and shadows. Ahigher number of struts 2204 can increase radial force.

FIG. 22C illustrates another example of an anchor 2220. FIG. 22Cillustrates a collapsed or delivery state of the anchor 2220. FIG. 22Dillustrates a deployed state of the anchor 2220. The anchor 2220comprises a plurality of struts 2224 that are twisted around thetransducer 2221. The plurality of struts 2224 may be collapsed anddeployed via any of the methods described herein (e.g., self-expanding,umbrella-type, and combinations thereof). The twisted configuration ofthe plurality of struts 2224 can reduce the overall interference orultrasound shadows that the plurality of struts 2224 may create acrossthe transducer assembly 2221. For example, there is less interferenceproduced in the longitudinal direction by each strut 2224 because thetwisted configuration will only cover a portion of the transducerassembly 2221 in the longitudinal direction instead of an entire sectionof the transducer assembly 2221 in the longitudinal direction.

As shown in FIG. 22D, along any longitudinal line, there may be aportion of one or several struts 2224, but there is no longitudinal linethat is entirely a strut. The twisted configuration allows for coverageby the struts 2224 to be positioned in various sections of thetransducer assembly 2221, such that entire longitudinal sections are notcovered. Combined with the application of power to the length of thetransducer assembly 2221 and the focusing provided by the lens, atwisted configuration of the plurality of struts 2224 may increase theprobability of all the targeted tissue (e.g., including nerves) beingablated due to the reduction in potential interference or shadows causedby the struts 2224. Twisted struts 2224 can provide a partially lateraldimension to the anchor 2220, which can help to provide better vesselwall apposition, for example providing a counter force to longitudinalblood flow. Straight struts 2204 may be less prone to cause bloodturbulence. The various strut configurations described herein may beimplemented in other catheter systems described herein, e.g., cathetersystem 100.

FIGS. 23A and 23B illustrate an example transducer assembly including atransducer 2240 that is configured to slide over an inner shaft 2212when the anchor is deployed. When the anchor 2260 is deployed, thetransducer 2240 is translated across the inner shaft 2212 to ablateseveral ablation sites (e.g., a first ablation site 2242 a and a secondablation site 2242 b) at one anchoring position. The transducer 2240 maybe translated to one, two, three, four, five, or more ablation sites, ormore if desired, at one anchoring position. This method of translatingthe transducer 2240 can reduce treatment time by reducing the amount oftimes the anchor 2260 is collapsed and moved, and then redeployed withina vessel. In some embodiments, the anchor 2260 may be only partiallycollapsed or not collapsed before movement (e.g., it may be worthpossible vessel wall damage to reduce procedure time by moving an atleast partially expanded anchor). The transducer 2240 may be connectedto a pull and/or push wire 2244 to move the transducer 2240 along theinner shaft 2212.

FIGS. 23C to 23E illustrate an example method of rotating an anchor 2250between ablations. Rotation of the anchor 2250 may counteract or accountfor any interference caused by shadows created by the anchor 2250. Aftera first ablation conducted in a deployed state as shown in FIG. 23C, theanchor 2250 may be collapsed to a delivery state as shown in FIG. 23D.The anchor 2250 may then be rotated as shown by the arrow 2254. Theanchor 2250 is preferably not longitudinally moved during rotation. Theanchor 2250 is then redeployed with the struts touching a differentportion of the vessel wall, as shown in FIG. 23E. The struts of theanchor 2250 are in different positions than in FIG. 23C, which resultsin any interference or shadows occurring in different areas of thevessel, which can allow the transducer 2252 to ablate the tissue wherethe shadows were cast in FIG. 23C, thereby providing a more completeablation. This process will be repeated as many times as desired toaccount for interference or shadows.

FIG. 24A schematically illustrates an example embodiment of a catheter2400 comprising a handle 2404 and an elongate shaft 2402. A distalportion of the elongate shaft 2402 may comprise the transducer assembly,anchor, etc. The handle comprises an actuator 2406. The actuator 2406may be used to collapse and/or deploy the anchor 2400. The actuator 2406may comprise, for example, a thumb wheel or slider. In some embodimentsin which the actuator 2406 comprises a slider, the actuator 2406 canslide along a path 2410 in either direction, as indicated by the arrow2408. In some embodiments, the actuator 2406 can inform the operatorabout the inner diameter of a vessel. For example, as described herein,the longitudinal distance between the distal shaft 2402 and the proximalshaft 2412 is related to the radial expansion of the struts 2404. If theactuator 2406 proximally retracts the distal shaft 2402 by a certaindistance, then the corresponding extent of the radial expansion of thestruts 2404, and thus the diameter of the vessel that stopped expansionof the struts 2404, can be determined. The handle 2404 may compriseindicia along the path 2410. Vessel diameter information may be used toselect the energy value (e.g., time and/or modulation) to increase thesafety and the efficacy of the treatment.

In some embodiments, the handle 2404 may comprise a button 2412configured to start ablation. A foot switch, a software button locatedon an instrument touch screen, a mouse click, and/or other ablationinciting inputs are possible.

In embodiments comprising an outer sheath, the handle 2404 may comprisea mechanism to proximally retract and/or distally advance the outersheath (e.g., a second actuator). In some embodiments, the outer sheathmay be directly manipulated by the user (e.g., distal to the handle 2404and/or proximal to the handle 2404).

In some embodiments, the handle 2404 may comprise components forretracting the distal portion of the elongate shaft by a controlleddistance between ablation sites, as described in additional detailherein. For example, the handle 2404 may comprise a third actuator. Ifthe handle 2404 comprises a plurality of actuators, the actuators may belabeled with indicia (e.g., letters or numbers), comprise differentcolors, etc. Preferably, each of the actuators is at least partiallydifferent. For example, a plurality of actuators each configured toslide in a path may have different shapes, surface textures, colors,etc. In some embodiments, the actuators are distinguishable by beingdifferent types of actuators (e.g., thumb wheel for operation of theouter sheath, slider for deployment of the anchor, knob for controlledretraction of the distal portion, etc.).

FIG. 24B schematically illustrates another example embodiment of acatheter 2420 comprising a handle 2424 and an elongate shaft 2402. Thehandle 2424 may comprise the features of the handle 2404. The handle2424 comprises a proximal part 2426 and a distal part 2428. The proximalpart 2426 may be rotated relative to the distal part 2428 as shown bythe arrow 2422 to advance or retract the distal portion of the catheter2420 within a vessel. The rotation of the proximal part 2426 istranslated into linear motion advancing or retracting the distal portionof the catheter 2420 within a vessel, for example using a helix, a wormgear, rack and pinion, etc. Rotating the proximal part 2426 in onedirection advances the distal portion of the catheter 2420, and rotatingthe proximal part 2426 in the opposite direction retracts the distalportion of the catheter 2420. The handle 2424 may comprise detents tohelp the user determine an appropriate amount of rotation and thusmovement of the distal portion of the catheter 2420. For example, eachcontrolled turn of the proximal part 2426 may proximally retract thedistal portion of the catheter a set distance, for example between about0.25 cm and about 2 cm (e.g., about 0.25 cm, about 0.5 cm, about 1 cm,about 1.5 cm, about 2 cm, and ranges between such values). Distaladvancement of the distal portion is also possible.

In some embodiments, the distal portion of the catheter 2420 is advancedto a first target location, such as a distal location in the LPA. Theanchor is deployed and the tissue around the first target location isablated. The anchor is then collapsed and the proximal part 2424 isrotated to proximally retract the distal portion of the catheter 2420,for example by 0.5 cm, to a second target location. The handle 2424 maycomprise an interlock that inhibits or prevents rotation of the proximalpart 2426 if the anchor is in a deployed state. The anchor is redeployedand the tissue around the second target location is ablated. Thiscollapse, retract (or otherwise move), redeploy, ablate sequence can berepeated for the length of the LPA and then the length of the PT. Thedistal portion of the catheter 2420 is then advanced to an nth targetlocation, such as a distal location in the RPA (e.g., after usermanipulation of a guidewire). The anchor is redeployed and the tissuearound the nth target location is ablated. The collapse, retract (orotherwise move such as distally advance), redeploy, ablate sequence canbe repeated for the length of the RPA. The handle configurationsdescribed herein may be implemented in other catheter systems describedherein, e.g., catheter system 100.

Any sequence of treatment of pulmonary arteries is possible. Forexample: LPA, then PT, then RPA; RPA, then PT, then LPA; LPA, then RPA,then PT; RPA, then LPA, then PT; PT, then RPA, then LPA; PT, then LPA,then RPA. Preferably, the PT is ablated after the LPA or the RPA toreduce navigation. In some embodiments, the PT may be ablated after theLPA and after the RPA.

FIGS. 25A and 25B illustrate another example embodiment of an anchor2500. FIG. 25A illustrates the anchor 2500 in a collapsed state. In someembodiments, an outer sheath 2510 inhibits or prevents the anchor 2500from expanding while in the collapsed state. FIG. 25B illustrates theanchor 2500 in a deployed state. The anchor 2500 comprises components oneach side of the transducer assembly 2501. The anchor 2500 comprises twobraid configurations 2502. Additional braid configurations 2502 are alsopossible. The first braid configuration 2502 is distal to the transducerassembly 2501, and the second braid configuration 2502 is proximal tothe transducer assembly 2501. Braid configurations 2502, for examplehaving a high braid angle, can provide superior radial force compared toa plurality of struts having similar thicknesses, etc.

FIGS. 26A and 26B illustrate another embodiment of an anchor 2600. FIG.26A illustrates the anchor 2600 in a collapsed state. In someembodiments, an outer sheath inhibits or prevents the anchor 2600 fromexpanding while in the collapsed state. FIG. 26B illustrates the anchor2600 in a deployed state. The anchor 2600 comprises a plurality ofstruts 2602 on each side of the transducer assembly 2601. The anchor2600 comprises two pluralities of struts 2602. Additional pluralities ofstruts 2602 are also possible. The plurality of struts 2602 may beconfigured and operate in any of the ways the plurality of struts 2204are described herein. For example, the size and shape of the struts 2602may be any of the embodiments described herein, and the deploying andcollapsing of the anchor 2600 may occur in any of the ways describedherein. Pluralities of struts 2602 can provide simpler and/or morerepeatable manufacturing compared to braid configurations 2502, forexample in terms of coupling to proximal and/or distal shafts.

In some embodiments, the anchor 2500, 2600 is deployed by pushing thebraid configurations 2502 or the pluralities of struts 2602 together,causing the braid configurations 2502 or the pluralities of struts 2602to bow radially outwards, as shown in FIGS. 25B and 26B. In someembodiments, the anchor 2500, 2600 is self-expanding. The anchor 2500,2600 may be collapsed and deployed by moving an outer sheath 2510 (FIGS.25A and 25B) to cover or expose the anchor 2500, 2600. The outer sheath2510 is moved in the direction of the arrow 2506 to deploy the anchor2500, 2600. Additionally or alternatively, the anchor 2500, 2600 may becollapsed and deployed via a pull wire connected to one, some or all ofthe braid configurations 2502 or the pluralities of struts 2602. Theanchor 2500, 2600 deploys when the pull wire(s) are pulled, and theanchor 2500, 2600 collapses when the pull wire(s) are advanced. Inaddition to or alternative to a pull wire, a shaft or tube could be usedto push and/or pull a proximal and/or distal part of an anchor to deployand/or collapse the anchor. In some embodiments, the pull wire(s) may bebiased towards the collapsed state for a fail-collapsed configuration.In some embodiments, the fail-collapsed configuration could be achievedby heat shaping the anchor in the collapsed configuration. In certainsuch embodiments, a push mechanism could be used to achieve the deployedconfiguration. The anchor may be actuated and/or kept actuated by awheel locker in a handle. Being fail-collapse can collapse the anchorupon failure (e.g., of the wire, shaft, etc.) while deployed in thesubject.

FIGS. 27A to 27D illustrate another embodiment of an anchor 2700. FIG.27A illustrates the anchor 2700 in a collapsed state. In the embodimentillustrated in FIG. 27A, the outer sheath 2710 is inhibiting orpreventing the anchor 2700 from radially expanding, for example causingstress-induced martensite. FIG. 27B illustrates the anchor 2700 in adeployed state. When the petal configurations 2702 are not confined bythe outer sheath 2710, the anchor 2700 can self-expand due to a phasechange to austenite. The anchor 2700 comprises a petal configuration2702 on each side of the transducer assembly 2701. The anchor 2700comprises two petal configurations 2702. Additional petal configurations2702 are also possible.

The petal configurations 2702 comprise one or more wires shaped as aflower with multiple petals 2706. The petals 2706 may circumferentiallyoverlap. The wire(s) may be shape set in the deployed state so that thepetal configurations 2702 are self-expanding. In some embodiments, theanchor 2700 includes a float section (e.g., a segment generally parallelto the longitudinal axis) at the tip of the petals to increase thecontact surface between the anchor 2700 and the vessel wall. Theincrease in contact surface may reduce the radial force applied to thevessel wall while still achieving the same anchoring (e.g., providing asubstantially constant transducer assembly 2701 position under the sameforces such as blood flow).

The anchor 2700 may be configured in multiple orientations. The petalconfigurations 2702 may be oriented to open facing the distal portion ofthe catheter, for example as shown in FIG. 27B. The petal configurations2702 may be configured to face the handle (e.g., as described herein) ofthe catheter, for example as shown in FIGS. 27A to 27D. The petalconfigurations 2702 may be configured to face each other. The petalconfigurations 2702 may be configured to face away from each other.

The anchor 2700 may be self-expanding. The anchor 2700 may be collapsedand deployed by moving an outer sheath 2710 to cover or expose the petalconfigurations 2702. In some embodiments, the anchor 2700 is collapsedand deployed via a pull wire. If a petal configuration 2702 faces thehandle, a pull wire may be used to collapse the petal configuration 2702that is not collapsible by an outer sheath 2710 due to the direction thepetal configuration 2702 is facing.

FIG. 27C is a top view of an example petal configuration for the anchor2700 of FIG. 27A. The petals may have a circumferential width 2720between about 5 mm and about 15 mm (e.g., about 5 mm, about 7 mm, about9 mm, about 11 mm, about 13 mm, about 15 mm, and ranges between suchvalues). The base of the petal configurations may be configured tocreate angles 2722 of between about 10 degrees and about 20 degrees(e.g., about 10 degrees, about 12 degrees, about 14 degrees, about 16degrees, about 18 degrees, about 20 degrees, and ranges between suchvalues).

FIG. 27D is a side view of the example petal configuration of FIG. 27A.The top portion of the petals may have a radius 2724 between about 1 mmand about 8 mm (e.g., about 1 mm, about 2 mm, about 3 mm, about 4 mm,about 5 mm, about 6 mm, about 7 mm, about 8 mm, and ranges between suchvalues). The distance 2726 between the base of the petal configurationand the center of the diameter of the petals may be between about 12 mmand about 20 mm (e.g., about 12 mm, about 14 mm, about 16 mm, about 18mm, about 20 mm, and ranges between such values). The distance 2728between the base of the petal configuration and start of the petals maybe between about 2 mm and about 8 mm (e.g., about 2 mm, about 3 mm,about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, and rangesbetween such values). The distance 2730 between the angle portion of thepetal and the start of the arc of the petal may be between about 0.5 mmand about 2.5 mm (e.g., about 0.5 mm, about 1 mm, about 1.5 mm, about 2mm, about 2.5 mm, and ranges between such values).

The anchors 2500, 2600, 2700 can apply a radial force on the vessel wallto anchor the transducer assembly 2501, 2601, 2701 within the vessel.The anchor 2500, 2600, 2700 is configured to conform to the differentdiameters of the vessels, as described herein. For example, the PT istypically larger in diameter than the LPA and RPA and the anchor 2500,2600, 2700 expands according to the diameter of the ablation site.Depending on the diameter of the vessel, it may not be possible toachieve the delivery states shown in FIGS. 8B, 9B, and 10B, butexpansion of the anchor 2500, 2600, 2700 such that the anchor 2500,2600, 2700 is able to maintain a substantially constant position of thetransducer assembly 2501, 2601, 2701 in the vessel may be considered thedeployed state. Ablation preferably occurs when the anchor 2500, 2600,2700 is in the deployed state, or is not in the delivery state.

The anchors 2500, 2600, 2700 are proximal and distal to the transducerassemblies 2501, 2601, 2701, respectively. The anchors 2500, 2600, 2700do not longitudinally overlap with the transducer assemblies 2501, 2601,2701 and do not cast shadows, scatter acoustic energy, or otherwiseblock ablation energy. The anchors 2500, 2600, 2700 can allow a singleablation without rotation because the ablation energy can becircumferential and not blocked.

FIGS. 25A and 25B illustrate two braid configurations 2502, FIGS. 26Aand 26B illustrate two pluralities of struts 2602, and FIGS. 27A to 27Dillustrate two petal configurations 2702, but some embodiments ofanchors may comprise any number of braid configurations, pluralities ofstruts, petal configurations, combinations thereof, and/or the like. Forexample, an anchor may comprise one braid configuration and oneplurality of struts, one braid configuration and one petalconfiguration, or one plurality of struts and one petal configuration,for example to provide certain benefits of each type of anchor.

FIGS. 28A to 28D illustrate another embodiment of an anchor 2800. FIG.28A illustrates the anchor 2800 in a collapsed state. FIG. 28Billustrates the anchor 2800 in a deployed state. The anchor 2800comprises one petal configuration 2802. The petal configuration 2802 maybe configured in any of the described embodiments of petalconfigurations 2702.

The anchor 2800 can be configured with the petal configuration 2802facing proximally. When the petal configuration 2802 is proximal to thetransducer assembly 2801, the petal configuration 2802 faces away fromthe transducer assembly 2801 (e.g., as shown in FIG. 28B). When thepetal configuration 2802 is distal to the transducer assembly 2801, thepetal configuration 2802 faces towards the transducer assembly 2801. Theanchor 2800 may be deployed and collapsed via an outer sheath 2810and/or pull wire(s) 2804 connected to one, some, or all of the petals ofthe petal configuration 2802. If the pull wire(s) 2804 is not connectedto all petals, the overlapping of the petals can cause all petals to becollapsed when the pull wire 2804 is pulled. FIGS. 28C and 28Dillustrate the use of an outer sheath 2810 to deploy and collapse theanchor 2800. The outer sheath 2810 is positioned on the distal portionof the catheter. The outer sheath 2810 is distally advanced in thedirection of the arrow 2808 to allow the anchor 2800 to expand to thedeployed state. The outer sheath 2810 is then proximally retracted tocollapse the anchor 2800.

FIGS. 29A and 29B illustrate another embodiment of an anchor 2900. FIG.29A illustrates anchor 2900 in a collapsed state. In the embodimentillustrated in FIG. 29A, outer sheath 2910 is inhibiting or preventinganchor 2900 from radially expanding. For example, anchor 2900 mayinclude ring balloon 2902 coupled to a plurality of self-expandingstruts 2904. Struts 2904 may be coupled to ring balloon 2902 at equallyspaced locations along the circumference of ring balloon 2902. FIG. 29Billustrates anchor 2900 in a deployed state. When ring balloon 2902 andstruts 2904 are not confined by outer sheath 2910, struts 2904 mayself-expand. In addition, ring balloon 2902 may be inflated, e.g., viaan inflation lumen extending through one of the struts of plurality ofstruts 2904, to fully deploy anchor 2900 such that ring balloon 2902contacts the inner wall of the blood vessel, to thereby centralizetransducer 2901 within the blood vessel. Accordingly, the distancebetween tip 2911 and transducer 2901 may be minimized, and transducer2901 further may be positioned visually without additional movementduring anchor deployment. Moreover, anchor 2900 is coincident with thelocation of transducer 2901.

FIGS. 30A and 30B illustrate another embodiment of an anchor 3000. FIG.30A illustrates anchor 3000 in a collapsed state. Anchor 3000 includes aplurality of individually inflatable balloons 3002, each coupled to arespective struts of a plurality of struts 3004. Struts 3004 may eachinclude an inflation lumen for inflating balloons 3002. Moreover, anchor3000 includes sleeve 3006 circumferentially wrapped around balloons3002. FIG. 30B illustrates anchor 3000 in a deployed state. For example,anchor 3000 may be delivered to the target blood vessel within adelivery sheath, such that upon retraction of the sheath to exposeanchor 3000, balloons 3002 may be inflated, as shown in FIG. 30B, tothereby centralize transducer 3001 within the blood vessel. In thedeployed state, sleeve 3006 contacts the inner wall of the blood vessel,and blood is permitted to flow across anchor 3000 between balloons 3002and transducer 3001. Moreover, transducer 3001 may be positionedvisually without additional movement during anchor deployment, andanchor 3000 is coincident with the location of transducer 3001.

FIGS. 31A and 31B illustrate another embodiment of an anchor 3100. FIG.31A illustrates anchor 3100 in a collapsed state. Anchor 3100 includescoil 3102 circumferentially wrapped around the longitudinal axis ofanchor 3100. A distal end of coil 3102 may be coupled to tip 3111disposed at the end of inner catheter 3104, and a proximal end of coil3102 may be coupled to the distal end of outer catheter 3110, whereininner catheter 3104 is slidably movable within outer catheter 3110.Accordingly, relative movement between inner catheter 3104 and outercatheter 3110 may cause coil 3102 to transition between a collapsedstate, as shown in FIG. 31A, and a deployed state, as shown in FIG. 31B,by moving the proximal and distal ends of coil 3102 toward and away fromeach other. In some embodiments, coil 3102 may be self-expanding, e.g.,biased toward the deployed state. Moreover, transducer 3101 may bepositioned visually without additional movement during anchordeployment, and anchor 3100 is coincident with the location oftransducer 3101.

FIGS. 32A and 32B illustrate another embodiment of an anchor 3200. FIG.32A illustrates anchor 3200 in a collapsed state. In the embodimentillustrated in FIG. 32A, outer sheath 3210 is inhibiting or preventinganchor 3200 from radially expanding. For example, anchor 3200 mayinclude proximal coil 3202 a disposed between catheter 3204 andtransducer 3201, and distal coil 3202 b disposed between tip 3211 andtransducer 3201. Proximal coil 3202 a and distal coil 3202 b may beformed of a shape memory metal, e.g., Nitinol, such that proximal coil3202 a and distal coil 3202 b are biased toward the expanded state. Uponretraction of sheath 3210, proximal coil 3202 a and distal coil 3202 bmay transition to the expanded state, as shown in FIG. 32B, to therebycentralize transducer 3201 within the blood vessel.

FIGS. 33A to 33D illustrate another embodiment of an anchor 3300. Theanchor 3300 comprises a loop wire 3302. The anchor 3300 may compriseone, two, or more loop wires 3302. FIGS. 33C and 33D illustrate the loopwire 3302. FIG. 33A illustrates the anchor 3300 in a collapsed state. Anouter sheath as described herein may be used to inhibit or prevent theanchor 3300 from expanding. FIG. 33B illustrates the anchor 3300 in adeployed state.

The loop wires 3302 may be positioned distal and proximal of transducerassembly 3303 anchor the transducer assembly 3303 in a vessel. Inembodiments comprising a single loop wire 3302, the loop wire 3302 maybe located distal to or proximal to the transducer assembly 3303. Insome embodiments, the loop wire 3302 is self-expanding and can beactuated by pushing the wire (e.g., one or both legs) from the proximalside of the catheter. The loop wire 3302 is then collapsed by pullingthe wire.

All embodiments of the anchor described herein may be modified andcombined to create additional embodiments. For example, all embodimentsmay consist of one, two, three or four anchors. In embodimentscomprising more than one anchor, the anchors may be of different types.For example, one embodiment of an anchor may comprise a plurality ofstruts and a braid configuration. Any combination of the disclosedembodiments may be possible. All methods of deploying and collapsing thedifferent anchor embodiments may apply to any of the anchor embodiments,including but not limited to, the umbrella method, the movement of anouter sheath, the use of a pull wire, the use of actuating shafts (e.g.,telescoping shafts), and the use of self-expanding material. Inembodiments in which neuromodulation is provided by, for example,acoustic energy (e.g., ultrasound), microwave energy, radiofrequency(RF) energy, thermal energy, electrical energy, infrared energy, laserenergy, phototherapy, plasma energy, ionizing energy, mechanical energy,cryoablation, chemical energy, combinations thereof, and the like, theanchor may optionally push the transducer or other element against thevessel wall.

As described above, the distal portion of the catheter system (e.g.,distal region 104 of catheter system 100) is flexible enough tonavigates a variety of vessels, and cavities such as heart chambers, andrigid enough to be advanced through valves such as the tricuspid valveand the pulmonary valve. This combination of flexibility and rigiditymay cause undesirable effects when the distal portion is anchoredablation. FIG. 34A illustrates an example catheter in a vessel 3401 thatis not properly anchored. As shown in FIG. 34A, the transducer assembly3420 is supposed to be anchored for ablation. The curvature of thecatheter proximate to the anchor pushes the transducer assembly 3420 tothe right side because the radial force of the anchor is not able toovercome the force of the catheter.

FIG. 34B illustrates an example embodiment of a catheter in which thestiffness of the shaft 3400 can be effectively negated proximate thedistal portion. To reduce the impact of the shaft 3400 stiffness, someembodiments comprise a suspension 3402. The suspension 3402 may comprisea coil or other type of flexible shaft portion configured to releasesome of the constraints due to the shaft 3400 stiffness and curvatureproximate the distal portion. The suspension 3402 is more flexible thenthe shaft 3400, which can allow the distal portion to effectively ignorethe forces of the shaft 3400, which are absorbed by the suspension 3402.The suspension 3402 can provide better anchoring and centering of thetransducer assembly 3420. The suspension 3420 may comprise any suitablyflexible material.

The distal portion of the catheter system (e.g., distal region 104 ofcatheter system 100) may be navigated through vessels to multipleablation sites. The distance between ablation sites may be controlled(e.g., as described with respect to the handle 2424 and/or handle 300′)and/or monitored. The movement (e.g., retraction, advancement) featuresdescribed herein may be used to monitor the distance between ablationsites. FIG. 35A illustrates a distal portion of a catheter comprising ashaft 3510 and a transducer assembly 3520. The catheter is configured toenter the patient at a vein access point 3502. Vein access pointsinclude but are not limited to femoral, jugular, and radial accesspoints. Any suitable vein access point may be used.

The shaft 3510 may comprise electrodes 3504 located along a proximalportion of the shaft 3510. The electrodes 3504 are configured to sensethe electrical conduction between each electrode to determine thedistance the transducer assembly 3520 was pulled or pushed from anablation site. In some embodiments, the conduction between a first setof electrodes are high impedance, while the conduction between the restof the electrodes is low impedance. A variance between low and highimpedance may be used to account for the electrical conductivity of theblood that is in contact with the electrodes positioned within the body.For example, the electrodes 3504 outside the vein access point 3502 inFIG. 35A will have a high impedance, while the electrodes 3504 withinthe vein will have a lower impedance.

In some embodiments, the electrodes 3504 are located at fixed pointsalong the shaft 3510. The fixed locations allow software running on aninstrument (e.g., as described herein) to detect the number ofelectrodes 3504 moved in or out of the body. Tracking the movement ofelectrodes 3504 may be used to determine the approximate distancebetween positions of the transducer assembly 3520 and the differentablation sites. In some embodiments, data about the transducer assemblyposition, diameter of the deployed anchor, and/or ablation parameterscan be stored. A report can be produced. Reports from the treatment ofvarious subjects can be combined with data about the effectiveness ofthe treatment for those subjects to improve the system (e.g.,determining ideal ablation spacing, ablation parameters, etc.).Embodiments comprising electronics may comprise interlocks, for exampleinhibiting or preventing an ablation until the catheter has been movedto a different ablation site.

FIG. 35B illustrates another example embodiment of movement (e.g.,retraction, advancement) features. The shaft 3510 comprises marks orindicia 3506. Any number of marks 3506 along the shaft 3510 can be used.The marks 3506 can be separated any distance, for example every halfcentimeter. The marks 3506 allow the operator to control and monitor thedistance between two ablation sites when pulling or pushing thecatheter. For example, the marks 3506 may be compared to a stationaryobject (e.g., an access point). Some embodiments may include additionaland/or alternative methods to control the distance between two ablationsites when pulling or pushing the catheter. For example, an actuator(e.g., the actuator 2406 and/or pusher 1200) may be configured to pushor pull the catheter a specified distance with each actuation. Foranother example, magnetic beacons can be used. For another example, awheel with appropriate gearing can be used.

In some embodiments, the movement (e.g., retraction, advancement)feature may comprise radiopaque markers on the distal portion of thecatheter that can be observed under fluoroscopy. Such a movement featuremay provide the ability to make sure that the movement of the catheter(e.g., by manipulating a handle) translates into the expected or desiredmovement in the vessel. Fluoroscopy can also or alternatively be used incombination with any of the movement features described herein.

FIG. 36 is a schematic diagram of an example ablation instrument 3600.The instrument 3600 serves as the user interface and provides theelectrical power to a catheter 3608, e.g., catheter system 100. Theinstrument 3600 includes a display screen 3602, an ultrasound beamgenerator 3604, a power monitor 3605, a control computer 3606, aremovable catheter connector 3607 between the control computer 3606 anda catheter 3608, and a foot pedal 3610 that may be used to initiateablation. The display screen 3602 may be a touch screen. The instrument3600 may comprise other inputs (e.g., a mouse, a keyboard, a track ball,etc.).

The ultrasound beam generator 3604 comprises an electrical poweramplifier with an output between 1.5 MHz to 11 MHz capable of 200 Wattsor more of electrical power in continuous wave mode or in pulse wavemode. The ultrasound beam generator 3604 supports a programmaticinterface, for example through an internal USB to Serial port interface.The interface allows the control computer 3606 to start or stop theultrasound emission. The ultrasound beam generator 3604 can embed afirmware in charge of the pulse emission communication with the controlcomputer 3604 to check internal devices such as temperature sensors(e.g., as described herein), fans, etc.

The tissue around the pulmonary artery, which may include nerves, can beablated by applying ultrasound energy to the transducer, which isfocused by the lens. The energy can be applied for a duration betweenabout 0.5 seconds and about 1 minute (e.g., about 0.5 seconds, about 1second, about 2 seconds, about 3 seconds, about 4 seconds, about 5seconds, about 6 seconds, about 7 seconds, about 8 seconds, about 9seconds, about 10 seconds, about 15 seconds, about 30 seconds, about 45seconds, about 1 minute, and ranges between such values).

The energy can be between about 20 Watts (W) and about 80 W acoustic(e.g., about 20 W, about 30 W, about 40 W, about 50 W, about 60 W, about70 W, about 80 W, and ranges between such values). The acoustic wattageis at least partially based on electric power applied and the efficiencyof the system such as the transducer assembly. For example, if thesystem is 50% efficient, the application of 40 W electric would be 20 Wacoustic. If transducer assemblies are between about 50% and about 80%efficient, then the electrical power applied can be between about 25 Wand about 160 W to produce between about 20 W and about 80 W acoustic.

Although described herein with respect to ultrasound, other energymodalities are also provided, for example unfocused ultrasound, focusedultrasound such as high-intensity or low-intensity focused ultrasound,microwave energy, radiofrequency (RF) energy (e.g., monopolar, bipolar,etc.), thermal energy (e.g., cryoenergy, heat or cold provided by afluid (e.g., water, saline, liquid medicament, etc.) or gas (e.g.,steam)), electrical energy (e.g., non-RF electrical energy), infraredenergy, laser energy, phototherapy or photodynamic therapy (e.g., incombination with one or more activation agents), plasma energy, ionizingenergy delivery (e.g., X-ray, proton beam, gamma rays, electron beams,alpha rays, etc.), mechanical energies delivered by cutting or abrasiveelements, cryoablation, chemical energy or modulation (e.g.,chemoablation), or combinations thereof. In some embodiments, disruptionor interruption of nerves is carried out by chemicals or therapeuticagents (for example, via drug delivery), either alone or in combinationwith an energy modality. In some embodiments, pharmaceuticals arecombined with the neuromodulation (e.g., ablation) described herein toreduce the dosage or duration of pharmacology therapy, thus reducingside effects. In various embodiments, different energy modalities may beused in combination (either simultaneously or sequentially).

The power monitor 3605 measures the electrical power using a directionalcoupler. The directional coupler comprises two coils with ferrite tomeasure power without inducing a loss due to measurement. The powermonitor 3605 measures the power being sent to the transducer (forwardpower) and the power being reflected back (reverse power). The forwardor the reverse power are measured through an Analog to Digital Converterthat are read in real-time by the control computer through an internalUSB interface.

The efficiency and natural frequency of each catheter, transducer,and/or transducer assembly may be measured prior to use, for example bythe manufacturer, another facility, an independent company, and/or thelike.

During the ablation procedure, the user inputs the efficiency and thenatural frequency of the transducer being used. Each system can includean indicator of the efficiency of that particular system so that theultrasound beam generator can account for losses to deliver theappropriate acoustic energy. The indicator may be a fact sheet that isinput by a user. The fact sheet may be a sticker on the box, on theinstructions for use, on a sterile wrapper, on a package insert, and/orthe like. The indicator may be a bar code or QR code that may be read byan appropriate device. The indicator may be embedded in a flash memorysuch as an EPROM that can be automatically read by the ultrasound beamgenerator when the catheter 3608 is coupled to the connector 3607. Thememory may be in a USB stick, a SD card, or other hard media that may berequired to be inserted in the control computer 3606 for the system tofunction. The beam generator can use information from the indicator toensure that a catheter is not reused for multiple procedures (e.g., atall, unless a user indicates appropriate sterilization, etc.). A simplerindicator may reduce costs. A more complicated indicator can reduce therisk of user error.

During use, the power monitor 3605 will monitor the reverse power(unused power that is reflected back) and compare it to the expectedresults from the inputted data. If the reverse power losses arecalculated as being too high or indicate a broken transducer (or anyproblem with the transducer), the procedure can be stopped. For example,if there is too much reverse power, the energy is not converted intoacoustic and therefore the system is in some variety of failure (e.g.,broken cable linking generator and transducer, solder failure, too manybubbles reflecting the power back to the source, parasitic capacitance,etc.).

The control computer 3606 is configured to assist the user during aprocedure. The control computer 3606 controls the user interface, drivesthe power generator, and controls the power output. For example, thecontrol computer 3606 may be loaded with data from a planning tool toassist in ablation. This data may comprise ablation site positions,diameters of the vessels, distances between ablation sites, etc. Thepre-loaded data may comprise data that was previously collected via CTscan images, MRIs, IVUS, or other medical scans, images, tests of thepatient, etc. By knowing this information prior to the procedure, theuser may define the diameter of the artery at the ablation site usingthe control computer 3606 to set or optimize the acoustic power and thepulse duration. After the initial phase of positioning the catheter, thetreatment may then be automatically monitored using the electrodes,described herein, to generate a treatment report.

The treatment report may include a report of the power delivered at eachablation site. A report of the power delivered will increase the user'soverall efficiency and capability from procedure to procedure. Thereport may also indicate the different sizes of toroidal ablation basedon vessel size. For example, the smaller the vessel, the smaller thetoroidal ablation site should be. If the reported size varies from theexpected size, the user may adapt the power or time of ablation based onthe vessel size. In some embodiments, the anchor may be configured tomeasure the vessel size to be included in the treatment report.

Sensors (e.g., sensor 3700) may be used to monitor different valuesduring ablation. FIG. 37A illustrates an example catheter 3702comprising a sensor 3700 located on a distal portion of a catheter 3702.The sensor 3700 may be positioned distal to the transducer 3704, asshown, proximal to the transducer 3704, or in any other suitableconfiguration. The sensor 3700 may be configured to monitor temperatureto track safety and efficiency of the ablation procedure.

FIG. 37B is a graph depicting temperature measurement 3710 and pulseemission 3708 during ablation. As shown in FIG. 37B, the temperaturemeasurement 3710 should be consistent while ablating. The pulse emission3708 should also be consistent during ablation. The sensor may beconfigured to indicate if there is a change in temperature or anunexpected temperature. For example, a temperature that is too high mayindicate that there is something wrong and that the procedure should bestopped. The temperature measurement samples in between two pulseemissions 3708 may work around the viscous heating effect of thethermocouple measurement while the thermocouple is located inside theultrasound beam. This viscous heating effect can be an artifact thatrises the temperature value and could lead to wrong measurement. Thesensor 3700 may also be configured to measure other values such as bloodpressure, flow rate, heart rate, and/or any measurement that may berelevant to the procedure or safety of the patient. Any measurementstaken, such as blood pressure, may be used to synchronize the ultrasoundemission with the measurement taken.

In some embodiments, the transducer assembly could be used to measurethe efficiency by measuring a returned signal during theneuromodulation. For example, during a pulse emission, some energy isreflected back to the transducer when the ultrasound wave travelsthrough an interface between media. When tissue heats, thecharacteristic of that medium changes, and the change in the energyreflected back from an interface including that medium can be detectedusing the transducer as a sensor. The reflected energy may change theimpedance of the transducer assembly, which can induce a modification ofthe reflected power returned back to the generator. The reflected powersignal analysis can be used to detect a threshold when the pulse startsto be efficient enough, for example, to ablate the tissue. Thisinformation could be used to stop the pulse emission when the heating issufficient for the nerve denaturation. In some embodiments, amultielement ultrasound probe having a cylindrical shape could be addedto the system, separate from the transducer used for theneuromodulation, to perform ultrasound thermometry from the inside ofthe lumen and inform on the procedure efficacy.

FIG. 37C illustrates an example catheter system including a secondcatheter 3724 embodiment comprising a sensor 3722. The second catheter3724 is separate from the catheter 3726 comprising the transducer. Thesensor 3722 being on a second catheter 3724 can increase the flexibilityof where measurements may be taken. For example, the second catheter3724 may be positioned in a different vessel than the first catheter3726 or in a different location within the same vessel as the firstcatheter 3726. In some embodiments, the first catheter 3726 may comprisea lumen (e.g., having an exit port proximal to the transducer) to helpguide the second catheter 3724 proximate to its intended position.

FIG. 37D illustrates a sensor 3730 coupled to the interior of a lens3732. The sensor 3730 is configured to measure the lens temperature. Thesensor 3730 may be a thermocouple sensor. This temperature may bemonitored to inhibit or prevent overheating of the transducer 3734 toprotect the transducer 3734 from being damaged. The temperature of thelens 3732 may be monitored because a lens that has too high atemperature may create clots in a patient.

FIG. 37E illustrates a plurality of sensors 3740 located on an anchor3742. The sensors 3740 may be thermocouple sensors. One sensor 3740 maybe used. In some embodiments, one, some, or all of the struts or othercomponents (e.g., petals) comprises a sensor 3740. In some embodiments,some struts comprise a sensor 3740. The sensors 3740 may be used tomeasure the temperature next to a vessel wall.

Ablation using any embodiment of the device described herein may occurat multiple ablation sites using a collapse and deploy method. FIG. 38Aillustrates the positioning of a first catheter 3804 in a vein 3808 atan insertion site or vein access point 3806. The first catheter 3804 maycomprise a balloon 3802. The first catheter 3804 may be positioned inthe vein 3808, and the balloon 3802 may then be inflated. The inflatedballoon 3802 may then be carried by blood in the venous vasculature,through the right heart, and to a first pulmonary artery. A guidewire3812 may then be navigated to the first pulmonary artery and the firstcatheter 3804 may be removed, and described above with regard to step704 of method 700. FIG. 38B illustrates a treatment catheter 3804 beingpositioned over the guidewire 3812. The treatment catheter 3804 istracked over the guidewire 3812 to the first pulmonary artery, anddescribed above with regard to step 710 of method 700. The treatmentcatheter 3804 may be any of the previously described embodiments.

FIG. 38C illustrates the distal portion of the shaft of the treatmentcatheter 3804 being positioned within the right pulmonary artery (RPA)3820. The anchor 3822 has been positioned and deployed, according to anyof the methods described herein, e.g., step 712 of method 700, withinthe RPA 3820 at a first ablation site. The anchor 3822 anchors thetransducer 3826 within the RPA 3820. The anchor 3822 deploys to contactthe artery wall 3824 applying a radial force. After deploying the anchor3822, the tissue surrounding the first ablation site (e.g., includingnerves) is ablated, and described above with regard to step 714 ofmethod 700. Interrupting the nerves around the RPA 3820 can reducepulmonary hypertension. In some embodiments, neuromodulation isaccomplished (e.g., via ablation, denervation, which may or may not bereversible, stimulation, etc.). Ablation may occur at one locationduring the deployed state, or the transducer 3826 may be translated asdescribed herein to perform multiple ablations during a single deployedanchor position.

An ablation site may be ablated for between about 0.5 seconds and about1 minute (e.g., about 0.5 seconds, about 1 second, about 5 seconds,about 30 seconds, about 1 minute and ranges between such values). Thefrequency used during ablation may be between about 1.5 MHz and about 11MHz (e.g., about 1.5 MHz, about 2 MHz, about 2.5 MHz, about 3.5 MHz,about 4.5 MHz, about 6 MHz, about 7.5 MHz, about 9 MHz, about 11 MHz,and ranges between such values). The acoustic power used during ablationmay be between about 20 W and about 80 W (e.g., about 20 W, about 30 W,about 40 W, about 50 W, about 60 W, about 70 W, about 80 W, and rangesbetween such values). This translates to electric power of between about25 W and about 160 W and ranges between such values.

Each ablation site may be of a different diameter. As shown in FIGS. 38Cto 38I, not all diameters of the pulmonary arteries are the same. Theanchor 3822 may be deployable to accommodate the different diameters, asdescribed herein. The locations being ablated may be at different depthsor focal points within the vessel walls. The ablation power and time orfrequency of the ultrasound beam may be varied to accommodate thevarying diameters and depths of the locations to be ablated. In someembodiments, a single set of ablation parameters (e.g., power, duration,frequency) could be used to accommodate various artery diameters. Forexample, the parameters (e.g., power, duration, frequency) could be setto a target range of lesion depth could be set to exclude tissue whereablation should not occur. In some embodiments, each ablation couldinclude 50 W for one minute followed by 100 W for at least 30 seconds,with optional additional pulses at 100 W for particular locations.

After a first ablation site has been ablated, the anchor 3822 iscollapsed by any of the methods described herein, e.g., step 716 ofmethod 700. The distal portion may then be retracted (or advanced) adistance within the RPA 3820, as shown by the arrow 3810 in FIG. 38C,and positioned and deployed at a second ablation site, as shown in FIG.38D. The deploying, ablating, collapsing, and retracting steps may berepeated until the tissue around the desired amount of the RPA 3820(e.g., the entire length of the RPA, ¾, ⅔, ½, ⅓, ¼, and ranges betweensuch values) has been covered by the ablation. Because nerves can actlike wires where cutting at any point along the length may be sufficientto disable the nerve, smaller lengths or segments of the RPA may beablated to have a beneficial effect. Because nerves are not necessarilystraight, can branch, can start or stop along the length of the RPA,etc. larger lengths may be used to have a beneficial effect. Ablationmay be repeated at some or all ablation sites to account for anyinterference or shadows caused by the anchors, as discussed herein.

FIG. 38E illustrates the distal portion of the shaft of the treatmentcatheter 3804 positioned within the left pulmonary artery (LPA) 3830.The anchor 3822 is positioned and deployed, according to any of theabove described methods, within the LPA 3830 at a first ablation site.The anchor 3822 anchors the transducer 3826 within the LPA 3830. Theanchor 3822 deploys to contact the artery wall 3832 applying a radialforce. After deploying the anchor 3822, the tissue surrounding the firstablation site (e.g., including nerves) is ablated. Interrupting thenerves around the LPA 3822 can reduce pulmonary hypertension. Ablationmay occur at one location during the deployed state, or the transducer3826 may be translated as described herein to perform multiple ablationsduring a single deployed anchor position.

Once the first ablation site has been ablated, the anchor 3822 may becollapsed by any of the methods described herein. The distal portion maythen be retracted (or advanced) a distance within the LPA 3830, as shownby the arrow 3812 in FIG. 38E, and positioned and deployed at a secondablation site, as shown in FIG. 38F. The deploying, ablating,collapsing, and retracting steps may be repeated until the tissue aroundthe desired amount of the LPA 3830 (e.g., the entire length of the LPA,¾, ⅔, ½, ⅓, ¼, and ranges between such values) has been covered by theablation. Because nerves can act like wires where cutting at any pointalong the length may be sufficient to disable the nerve, smaller lengthsor segments of the LPA may be ablated to have a beneficial effect.Because nerves are not necessarily straight, can branch, can start orstop along the length of the LPA, etc. larger lengths may be used tohave a beneficial effect. Ablation may be repeated at some or allablation sites to account for any interference or shadows caused by theanchors, as discussed herein.

FIG. 38G illustrates a transducer 3826 positioned within a pulmonarytrunk 3840 at a first ablation site. The anchor 3822 may be deployed byany of the described methods herein to anchor the transducer 3826 withinthe pulmonary trunk 3840. The anchor 3822 may be deployed to contact thepulmonary trunk walls 3842 applying a radial force to center thetransducer 3826. The first ablation site may be ablated. Interruptingthe nerves around the pulmonary trunk 3840 can reduce pulmonaryhypertension. The anchor 3822 may be collapsed by any of the methodsdescribed herein. The transducer 3826 may then be retracted (oradvanced) a distance within the pulmonary trunk 3820, as shown by thearrow 3814 in FIG. 38H, and positioned and deployed at a second ablationsite, as shown in FIG. 38I. The second ablation site may be ablated. Thedeploying, ablating, collapsing, and retracting steps may be repeateduntil the tissue around the desired amount of the pulmonary trunk 3840(e.g., the entire length pulmonary trunk, ¾, ⅔, ½, ⅓, ¼, and rangesbetween such values) has been covered by the ablation. Because nervescan act like wires where cutting at any point along the length may besufficient to disable the nerve, smaller lengths or segments of the PTmay be ablated to have a beneficial effect. Because nerves are notnecessarily straight, can branch, can start or stop along the length ofthe PT, etc. larger lengths may be used to have a beneficial effect.Ablation may occur at one location during the deployed state, or thetransducer 3826 may be translated as described herein to performmultiple ablations during a single deployed anchor position. Ablationmay be repeated at some or all ablation sites to account for anyinterference or shadows caused by the anchors, as discussed herein. Thetreatment catheter may then be removed from the patient.

This method of ablation may be performed in any order. For example, aspreviously described, the right pulmonary artery (RPA) may be ablatedfirst, followed by the left pulmonary artery (LPA), followed by thepulmonary trunk. Alternatively, the LPA may be ablated first, followedby the RPA, and followed by the pulmonary trunk. Any possible order maybe used. If needed, but not necessary, ablation sites may be repeated ineach vessel. For example, the pulmonary trunk may be ablated twiceand/or either or both of the pulmonary arteries may be ablated twice.

The device used during the ablation method may comprises any of theembodiments described herein. Any of the collapsing and deployingmethods described herein may be utilized. The movement featuresdescribed herein may also be utilized in monitoring the location of thedistal portion of the catheter 3804 when retracted or otherwise movedwithin a vessel.

While various illustrative embodiments of the invention are describedabove, it will be apparent to one skilled in the art that variouschanges and modifications may be made therein without departing from theinvention. The appended claims are intended to cover all such changesand modifications that fall within the true scope of the invention.

What is claimed:
 1. A method for reducing neural activity of nervesaround a blood vessel of a patient, the method comprising: measuringfirst pressure information within the blood vessel; applying a firstforce to an inner wall of the blood vessel to distend the blood vessel;measuring second pressure information within the blood vessel while thefirst force is applied to the inner wall to distend the blood vessel;emitting energy via an ablation device positioned within the bloodvessel to ablate nerves around the blood vessel; applying a second forceto the inner wall of the blood vessel to distend the blood vessel;measuring third pressure information within the blood vessel while thesecond force is applied to the inner wall to distend the blood vessel;and comparing the second pressure information to the third pressureinformation to determine whether the emitted energy has reduced neuralactivity of the nerves around the blood vessel.
 2. The method of claim1, wherein the second pressure information is indicative of a firstpressure gradient between pressure within the blood vessel while thefirst force is applied to the inner wall to distend the blood vessel andpre-distension pressure within the blood vessel associated with thefirst pressure information, and wherein the third pressure informationis indicative of a second pressure gradient between pressure within theblood vessel while the second force is applied to the inner wall todistend the blood vessel and pre-distension pressure within the bloodvessel associated with the first pressure information.
 3. The method ofclaim 2, wherein the emitted energy has reduced neural activity of thenerves around the blood vessel if the comparison of the second and thirdpressure information indicates that the second pressure gradient is lessthan the first pressure gradient by more than a predetermined threshold.4. The method of claim 2, wherein the emitted energy has reduced neuralactivity of the nerves around the blood vessel if the second pressuregradient is zero.
 5. The method of claim 1, wherein applying the firstand second force to the inner wall of the blood vessel to distend theblood vessel comprises applying a force sufficient to stimulatebaroreceptors within the blood vessel.
 6. The method of claim 1, whereinapplying at least one of the first or second force to the inner wall ofthe blood vessel to distend the blood vessel comprises expanding anexpandable member from a collapsed state to an expanded state, theexpandable member disposed on a catheter sized and shaped to bepositioned within the blood vessel.
 7. The method of claim 6, wherein,in the expanded state, the expandable member does not fully occludeblood through the blood vessel.
 8. The method of claim 6, wherein theablation device is disposed on the same catheter.
 9. The method of claim6, wherein the ablation device is disposed on a second catheter sizedand shaped to be positioned within the vessel, the second catheterdifferent from the catheter.
 10. The method of claim 1, wherein applyingat least one of the first or second force to the inner wall of the bloodvessel to distend the blood vessel comprises applying a torque to acatheter shaft to bend the catheter shaft within the blood vessel toapply the force.
 11. The method of claim 1, wherein, if the emittedenergy has not reduced neural activity of the nerves around the bloodvessel based on the comparison of the second and third pressureinformation, the method further comprises: emitting energy via theablation device positioned within the blood vessel to ablate nervesaround the blood vessel; applying a third force to the inner wall of theblood vessel to distend the blood vessel; measuring fourth pressureinformation within the blood vessel while the third force is applied tothe inner wall to distend the blood vessel; and comparing the fourthpressure information to at least one of the second or third pressureinformation to determine whether the emitted energy has reduced neuralactivity of the nerves around the blood vessel.
 12. The method of claim1, wherein emitting energy via the ablation device positioned within theblood vessel to ablate nerves around the blood vessel comprises emittingat least one of focused ultrasound, unfocused ultrasound, radiofrequency, microwave, cryo energy, laser, or pulsed fieldelectroporation.
 13. The method of claim 1, wherein emitting energy viathe ablation device positioned within the blood vessel to ablate nervesaround the blood vessel comprises emitting ultrasound.
 14. The method ofclaim 1, wherein the blood vessel is a pulmonary artery, and whereinemitting energy via the ablation device within the blood vessel reducesneural activity of nerves around the pulmonary artery to treat pulmonaryhypertension.
 15. The method of claim 1, wherein emitting energy via theablation device positioned within the blood vessel to ablate nervesaround the blood vessel comprises emitting energy via the ablationdevice in accordance with a predetermined actuation regime, thepredetermined actuation regime comprising predetermined periods ofnon-ablation between predetermined periods of ablation.
 16. The methodof claim 1, further comprising deploying an expandable anchor within thevessel to centralize the ablation device within the blood vessel. 17.The method of claim 16, wherein a first end of the expandable anchor iscoupled to a first catheter and a second end of the expandable anchor iscoupled to a second catheter slidably disposed over the first catheter,and wherein deploying the expandable anchor comprises moving the firstcatheter relative to the second catheter to cause the expandable anchorto transition from a collapsed state to an expanded state.
 18. Themethod of claim 17, wherein blood flow is permitted across theexpandable anchor in the expanded state.
 19. A system for reducingneural activity of nerves around a blood vessel of a patient, the systemcomprising: a catheter assembly comprising a proximal region operativelycoupled to a handle and a distal region sized and shaped to bepositioned within the blood vessel, the distal region of the catheterassembly comprising an ablation device configured to be actuated to emitenergy within the blood vessel to reduce neural activity of nervesaround the blood vessel; a distension mechanism configured to apply aforce to an inner wall of the blood vessel sufficient to distend theblood vessel and stimulate baroreceptors within the blood vessel; one ormore sensors configured to measure pressure within the blood vessel; anda controller operatively coupled to the one or more sensors, thecontroller programmed to: receive first pressure information within theblood vessel from the one or more sensors at a first time; receivesecond pressure information within the blood vessel from the one or moresensors at a second time while the distension mechanism applies a firstforce to the inner wall to distend the blood vessel; receive thirdpressure information within the blood vessel from the one or moresensors at a third time after energy is emitted within the blood vesselvia the ablation device to reduce neural activity of nerves around theblood vessel and while the distension mechanism applies a second forceto the inner wall to distend the blood vessel; and compare the secondpressure information to the third pressure information to determinewhether the energy has reduced neural activity of the nerves around theblood vessel.
 20. The system of claim 19, wherein the distensionmechanism comprises an expandable member configured to be expanded froma collapsed state to an expanded state to apply the force to the innerwall of the blood vessel.
 21. The system of claim 19, wherein thedistension mechanism comprises a torqueing mechanism configured to benda shaft of the catheter assembly within the blood vessel to apply theforce to the inner wall of the blood vessel.
 22. The system of claim 19,wherein the second pressure information is indicative of a firstpressure gradient between pressure within the blood vessel while thefirst force is applied to the inner wall to distend the blood vessel andpre-distension pressure within the blood vessel associated with thefirst pressure information, and wherein the third pressure informationis indicative of a second pressure gradient between pressure within theblood vessel while the second force is applied to the inner wall todistend the blood vessel and pre-distension pressure within the bloodvessel associated with the first pressure information.
 23. The system ofclaim 19, wherein the energy has reduced neural activity of the nervesaround the blood vessel if the comparison of the second and thirdpressure information indicates that the second pressure gradient is lessthan the first pressure gradient by more than a predetermined threshold.24. The system of claim 19, further comprising an expandable anchorconfigured to transition between a collapsed delivery state and anexpanded deployed state where the expandable anchor centralizes theablation device within the blood vessel.
 25. The system of claim 19,wherein the ablation device is configured to emit at least one offocused ultrasound, unfocused ultrasound, radio frequency, microwave,cryo energy, laser, or pulsed field electroporation.
 26. The system ofclaim 19, wherein the ablation device is configured to emit ultrasound.27. The system of claim 19, wherein the distension mechanism is disposedon the catheter assembly.
 28. The system of claim 19, furthercomprising: a second catheter assembly separate from the catheterassembly, wherein the distension mechanism is disposed on the secondcatheter assembly.
 29. The system of claim 19, wherein the catheterassembly comprises: an inner catheter comprising a guidewire lumenextending through at least a portion of a length of the inner catheter;a transducer shaft comprising a lumen sized and shaped to slidablyreceive the inner catheter therein, wherein the ablation device isdisposed on the transducer shaft; an outer catheter comprising a lumensized and shaped to receive the transducer shaft therein; an expandableanchor comprising a distal end coupled to the inner catheter and aproximal end coupled to the outer catheter such that relative movementbetween the inner catheter and the outer catheter causes the expandableanchor to transition between a collapsed delivery state and an expandeddeployed state, the expandable anchor configured to centralize theablation device within the blood vessel of the patient in the expandeddeployed state; and a sheath comprising a lumen sized and shaped toslidably receive the outer catheter and the expandable anchor in thecollapsed delivery state therein.
 30. The system of claim 29, wherein adistal region of the sheath has a stiffness sufficient to facilitatetransitioning of the expandable anchor from the expanded deployed stateto the collapsed delivery state upon movement of the distal region ofthe sheath relative to the expandable anchor without buckling the distalregion of the sheath.